Showing papers on "Tumor antigen published in 1977"

Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

Abstract: A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluoresence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care.

Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line

Abstract: Epidermoid cervical carcinoma cells (CaSki line) have been established in continuous culture. When leukocytes from cervical cancer patients were incubated with CaSki culture fluid concentrates, inhibition of leukocyte migration was observed in more than 70 percent of the patients tested. By contrast, significantly less inhibition was observed with normal donor leukocytes or leukocytes from patients with other types of cancer. These results were consistent with the expression of tumor-associated antigen by CaSki cells. Analysis of the serum from the donor of the cell line at the time of tumor biopsy, and of CaSki culture fluids, demonstrated the presence of the beta subunit of human chorionic gonadotropin.

Virus-specific proteins in the plasma membrane of cells lytically infected or transformed by pol-oma virus.

Abstract: Antisera, raised in rats, containing specificities directed against tumor antigen of polyoma virus also react with several proteins present in the plasma membrane of mouse cells infected with the virus. The main component has an apparent molecular weight of 55,000. The appearance of this protein after infection with early temperature-sensitive A mutants was temperature-dependent like tumor antigen itself. Pulse and chase isotope experiments suggest that this protein originates from a precursor, perhaps by cleavage; its production appears to be facilitated by the A mutation. Two other components with apparent molecular weights of 61,000 and 28,000 were also present but were more variable from experiment to experiment. All proteins were absent from the plasma membranes of cells infected with a transformation-defective mutant, NG-18. Up to four virus-specific proteins could be isolated from the plasma membranes of rat, hamster, and mouse cells transformed by the virus. The possible role of the plasma membrane proteins in cell transformation is discussed.

Antigenic Differences among Osteogenic Sarcoma Tumor Cells Taken from Different Locations in Human Tumors

Abstract: Sections were taken from the center, midzone, and margin of four human osteogenic sarcomas and one fibrosarcoma. Single-cell suspensions of tumors were examined in an indirect immunofluorescence assay with autologous or homologous anti-osteogenic sarcoma antisera as the intermediate reactant and fluorescein-labeled anti-human IgG as the final reactant. Cells were stained under conditions in which the fluorescence intensity was directly proportional to the density of the tumor-associated antigen on these cells. The density of tumor-associated antigen on cells from the center of the five tumor masses was low; cells from the midzone had intermediate levels of tumor antigen density, and cells at the margin had the highest levels. Similar preparations stained with polyspecific anti-HLA antisera did not demonstrate such a gradient. Since osteogenic sarcomas grow outward from the center, with the outer margin populated by the youngest cells, these results suggest that the oldest cells in the tumor bear the least tumor antigen, and the youngest tumor cells have the most. This is not compatible with theories which postulate that the immune system modulates the growth of a tumor so that only the least antigenic cells are allowed to grow. Alternative mechanisms are discussed.

Serologic Identification of Multiple Tumor-Associated Antigens on Murine Sarcomas

Abstract: The humoral immune response to two transplanted chemically induced murine sarcomas (MCA-2 and MCA-3) was studied in C57BL/6N mice. These tumors were immunogenic as evidenced by tumor amputation and rechallenge experiments, and no cross-reactivity between them was observed in in vivo challenge experiments. Utilizing a complement-dependent microcytotoxicity assay, we detected antibody to both MCA-2 and MCA-3 in the sera of animals bearing MCA-3 as well as after tumor removal. The sera of animals hyperimmunized to MCA-3 (MCA-3HI) was also cytotoxic in high titer to both MCA-2 and MCA-3 (50% cytotoxicity titers of 1:80 and 1:320, respectively). Sequential absorptions of sera from animals bearing MCA-3 and MCA-3HI sera with fresh MCA-2 cells completely removed activity against MCA-2 but retained reactivity to MCA-3. Sequential absorptions with fresh MCA-3 cells produced stepwise reductions of activity against both tumors, whereas absorption with normal cells produced no loss of activity against either tumor. Thus both specific and cross-reactive antigens were expressed on the surfaces of MCA-3 cells. Only the specific tumor antigen appeared to be involved in in vivo protection against tumor challenge.

An overview: Antitumor immunity in breast cancer assayed by tube leukocyte adherence inhibition

Abstract: The adherence to glass of human peripheral blood leukocytes (PBL) incubated with tumor antigen in vitro, is specifically inhibited if the PBL are sensitized to the antigen. The presence of leukocyte adherence inhibition (LAI) to tumor extracts indicates the presence of systemic antitumor immunity. By the tube leukocyte adherence inhibition assay (tube LAI), it was shown that 85% (191 of 223) Stage I and II, 45% (15 of 34) Stage III and 29% (30 of 103) Stage IV breast cancer patients had LAI reactivity. LAI responsiveness diminished with an increased tumor burden and most patients with advanced cancer exhibited no LAI reactivity. When LAI reactivity was monitored for 1 to 6 months after surgery, 13 of 25 Stage I and II breast cancer patients were negative on the first repeat assay. In general, 7 months after mastectomy most patients clinically free of cancer showed no LAI reactivity. Of thirty-five patients tested between 7 and 18 months after mastectomy, 6 were positive and 4 of the positives had local recurrence. The phenomenon of tube LAI appears to be mediated by monocytes armed with cytophilic antitumor antibody. The serum of patients whose leukocytes responded in the tube LAI assay had free cytophilic antitumor antibody that "armed" or sensitized normal leukocytes to respond in the LAI assay. Serum arming paralleled leukocyte reactivity before and after surgery. Patients with advanced cancer whose leukocytes failed to react in the LAI assay had serum blocking factors (excess tumor antigen) that abrogated the LAI reactivity of leukocytes from reactive patients.

Assignment of the integration site for simian virus 40 to chromosome 17 in GM54VA, a human cell line transformed by simian virus 40.

Abstract: GM54VA human cells transformed by simian virus 40 (SV40) were fused with peritoneal macrophages obtained from three different mouse strains. All 27 hybrid clones studied were positive for SV40 tumor antigen in 100% of their cells and contained human chromosome 17. Human chromosome 17 was the only human chromosome present in five of the hybrid clones. Fusion of GM54VA cells and either thymidine kinase (EC 2.7.1.75)-deficient mouse or Chinese hamster fibroblasts resulted in the growth in hypoxanthine-aminopterin-thymidine medium of hybrid clones positive and negative for SV40 tumor antigen. Counterselection of the hybrid clones positive for tumor antigen in medium containing 5-bromodeoxyuridine resulted in the growth of hybrid cells that were negative for tumor antigen. These experiments indicate that negative for tumor antigen. These experiments indicate that SV40 is integrated in only one of the two parental human chromosomes 17. Because the genome of SV40 has been assigned to human chromosome 7 in two other SV40-transformed human cell lines, at least two different integration sites for SV40 would seem to be present in human cells: one located in human chromosome 7 and the other located in human chromosome 17.

Tumor-associated antigen in bovine and ovine lymphosarcoma.

Abstract: Specific tumor-associated antigens were found on the membrane and in the cytoplasm of lymph node cells and peripheral blood lymphocytes (PBL) from cattle and sheep with lymphosarcoma by immunofluorescence tests. Materials from 15 cattle with the adult form of lymphosarcoma were examined. Cytoplasmic antigen was detected in fixed tumor cells from all 15 cases and in PBL from 9 cases tested. Membrane antigen was detected in living cells from 10 of the cases tested. In 3 calf-type cases, cytoplasmic antigen was found in a few (1 to 3%) of the tumor cells, while 1% of the cells from 2 thymic cases had cytoplasmic tumor antigen. In 15 cattle infected with bovine leukemia virus (BLV) but with no evidence of tumor, PBL from 3 cattle had the tumor-associated antigen in the cytoplasm. Negative results were obtained with similar tests done with 9 normal cattle that had no detectable BLV or BLV antibody. Cells from tumors induced with BLV in 5 sheep also had cytoplasmic antigen and membrane tumor-associated antigen. Tumor-associated antigen was found in PBL from 1 of 7 BLV-infected sheep with no clinical evidence of tumor. Similar tests were negative on 4 normal sheep.

Expression and thermal stability of simian virus 40 tumor-specific transplantation antigen and tumor antigen in wild type- and tsA mutant-transformed cells.

Abstract: We have explored aspects of a suggested relationship between the expression of simian virus 40 tumor-specific transplantation antigen (TSTA) and tumor antigen (TA) A unique rat embryo cell line transformed by a temperature-sensitive A mutant that loses TA during exposure to the nonpermissive temperature (A28-RE) was found to lose TSTA On the other hand, a typical control tsA-transformed cell line (A239-MB) expressed both TA and TSTA at the non-permissive temperature TA in lysates obtained from A239-MB cells was found to be three to four times more thermolabile by covwt-mb) when incubated at either 33 or 40 degrees C These data complement previous reports using TA from lytic infection and are consistent with the suggestion that TA is virus encoded In contrast to TA, which even in wild-type-transformed cells was completely destroyed in less than 10 min at 50 degrees C, TSTA, assayed in vivo by tumor rejection, and tumor-specific surface antigen(s) TSSA) defined by an in vitro cytolytic assay, were thermostabile Even after 24 h of incubation of extracts of 50 degrees C, high levels of TSTA and TSSA activity were present Since these surface antigens when obtained from cells transformed by tsA mutants were also thermostabile, they could not be distinguished from the wild-type antigens These results (i) indicate a coordinate expression of TA and TSTA in transformed cells; (ii) confirm that TA is virus encoded; and (iii) confirm that tha antigenic and immunogenic determinants that characterize TA and TSTA activities are distinct However, the possibility that TSTA, like TA, is of viral rather than cellular origin is not excluded

Induction of Simian Virus 40 (SV40) Transplantation Immunity in Mice by SV40-Transformed Cells of Various Species

Abstract: Specific tumor rejection was obtained with the use of simian virus 40 (SV40)-transformed cells from several species including man, rat, ape, sheep, and hamster. Growth of the syngeneic sarcoma mKSA in BALB/c mice was strikingly inhibited following a single immunization with as few as 10(3) intact, viable cells. Non-SV40-transformed cells did not induce tumor rejection activity nor did SV40-transformed lines induce immunity against the 3-methylcholanthrene-induced sarcoma Meth A, syngeneic with BALB/c mice. A close relationship existed between the tumor rejection antigen, the tumor-specific transplantation antigen (TSTA) located on the plasma membrane, and the intranuclear tumor antigen (T-ag). Both were associated with the DNA sequence of the early region of the SV40 genome, and TSTA activity was found in the nucleus. However, we did not observe a close parallelism between T-ag activity and TSTA. Neverthesless, the results strongly suggested that TSTA, like T-ag, was encoded by the virus.

Identification of simian virus 40 tumor and U antigens

Abstract: The synthesis and identity of the tumor and U antigens of simian virus 40 (SV 40) have been examined during productive infection in monkey cells, abortive infection in mouse cells, and in SV40-transformed mouse cells by using sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis to analyze [35S]methionine-labeled radioimmune precipitates. The following observations were made: (i) the tumor and U antigenic sites are on the same 94,000, 89,000, and 84,000 molecular weight species detected during productive infection; a 94,000 species made during abortive infection; and a 94,000 species found in transformed cells. (ii) The 94,000 species is relatively unstable compared to the relatively stable 89,000 and 84,000 species produced during productive infection. (iii) The stable 89,000 and 84,000 molecular weight species are differentially extracted from productively infected cells, which suggests an intracellular compartmentation and/or different affinities of these species for cellular substrates. (iv) The 94,000 species synthesized during abortive infection is more stable than the comparable 94,000 species synthesized in transformed cells. (v) Three tsA group mutants overproduce several unstable species of tumor antigen at restrictive temperature.

Cellular Immune Responses in Familial Medullary Thyroid Carcinoma

Abstract: We studied prospectively 46 members of a kindred with familial medullary thyroid carcinoma to determine the importance of possible cellular immune reactivity to tumor antigen. We evaluated in vitro production of macrophage-migration-inhibitory factor and 3H-thymidine uptake by lymphocytes from patients, family members and normal subjects in response to extracts of medullary thyroid carcinoma and normal thyroid tissue. Lymphocytes from 12 of 18 patients with medullary thyroid carcinoma and four of seven patients with C-cell hyperplasia produced migration inhibitory factor or proliferated (or both) in response to tumor antigen. In contrast, cells from only two of 25 normal subjects and two of nine family members not genetically at risk for medullary thyroid carcinoma made migration inhibitory factor and proliferated to tumor antigen. Of particular interest, lymphocytes from six of 12 clinically normal family members genetically at risk for medullary thyroid carcinoma exhibited cellular immune react...

Induction of tumor-immune responses and their interaction with the developing tumor.

Abstract: The central thesis of tumor immunology is that host responses to tumor-associated antigens exert a degree of immunological control over a developing tumor. This concept has developed principally from studies on experimental animal tumors induced by chemical carcinogens or oncogenic viruses, and to a lesser extent with naturally occurring tumors, in which it has been established that immunological rejection of tumors can sometimes be induced in suitably presensitized syngeneic recipients (Sjogren, 1965; Baldwin, 1973). Furthermore, immune rejection responses can be demonstrated in the tumor-bearing host, so that while the primary tumor implant is beyond host control, a concomitant challenge with the same tumor may be rejected, provided it is not too large (Gershon et al., 1967; Vaage, 1971). This has led to a further postulate, which proposes that the failure of immunocompetent hosts to reject a nascent tumor results from specific immune defects induced by tumor-associated products influencing primarily the cell-mediated arm of the tumor-immune response (I. Hellstrom and K.E. Hellstrom, 1969; K.E. Hellstrom and I. Hellstrom, 1974; Baldwin and Robins, 1975).

Detection of Soluble Tumor-associated Antigens in Serum of Tumor-bearing Rats and Their Immunological Role in Vivo

Abstract: Circulating soluble tumor antigens were detected in the serum of tumor-bearing rats. Sublethally irradiated W/Fu rats inoculated with syngeneic C58(NT)D Gross virus-induced lymphoma served as the source of tumor antigens. Soluble antigens were assessed by specific inhibition of the complement-mediated cytotoxicity of isogenic W/Fu anti-C58(NT)D antibodies against 51Cr tumor target cells. With a s.c. inoculum of 5 X 10(7) tumor cells, circulating tumor antigens were first detected at Day 8, and a maximum concentration was reached by Day 13 to 14, which coincided with the peak of tumor growth and was followed by the sudden death of the animals. Pooled serum from tumor-bearing rats was fractioned on Sephadex G-150 and resulted in one peak that contained all of the antigenic activity. The molecular weight of this fraction was estimated to be 50,000 to 60,000 daltons. Presensitization of normal rats with soluble tumor antigens resulted in a specific acceleration of tumor growth and delay in tumor rejection. Specificity was shown by lack of C58(NT)D tumor enhancement in rats presensitized with serum containing tumor antigens from a syngeneic but antigenically unrelated WR-6 lymphoma. The biological significance of circulating soluble tumor antigen mediating specific immunosuppression against an immunogenic tumor is discussed.

Purification of simian virus 40 tumor antigen from a line of simian virus 40-transformed human cells.

Abstract: Simian virus 40 tumor antigen can be isolated in a highly purified state from the nuclei ofSV80 cells, a continuous line of simian virus 40-transformed human fibroblasts. A five-step purification method was used. Its apparent molecular weight (in sodium dodecyl sulfate/polyacrylamide gels) is approximately 90,000-94,000. It contains a detectable amino-terminal residue.

Identification of a Tumor-Associated Antigen in Cervical Carcinoma by Two-Dimensional (Crossed) Immunoelectrophoresis

Abstract: Two-dimensional immunoelectrophoresis was used to evaluate 8 cervical cancer speciments, 11 other gynecologic tumors, and 5 specimens of normal cervix. Antigens were water-soluble tissue extracts and antisera prepared in rabbits. When tested against antisera to cervical cancer, cancer antigens showed 14-17 precipitin lines whereas normal cervix showed 10-16. A single heavy heterogeneous precipitin line with an electrophoretic mobility of 0.58 relative to bovine albumin was observed in all cervical cancer specimens but not in normal cervical or other tumor specimens. Further evidence for the uniqueness of this antigen was sought by enhancement (addition of another antigen to the first phase of electrophoresis which increased the size of common peaks) and suppression (addition of another antiserum to the second phase, whereby the peak size of components to which both sera have antibody was decreased). The specific precipitin line was neither suppressed by the addition of antisera to normal tissue nor enhanced when normal tissue antigen was added to the tumor antigen preparation. More conclusively, adsorption of the tumor antiserum with normal tissue had no effect on the unique tumor-associated precipitin line, whereas all other precipitin lines were removed. This antigen was common to other cervical tumors because enhancement was demonstrated with three other cervical tumor specimens. The identification of a distinct and separate antigen associated with cervical carcinoma will permit further characterization and possible development of immunodiagnostic methods.

Macrophage Processing of Antigen for Induction of Tumor Immunity

Abstract: Summary Previous studies have indicated, that, after in vitro incubation of antigen with macrophages, the “processed” antigen preferentially induces cell-mediated immunity. To investigate this phenomenon with tumor antigens, mycobacteria-stimulated macrophages were incubated with irradiated syngeneic EMT6 tumor cells for varying lengths of time and injected into normal mice. On subsequent challenge with EMT6, there was a significant increase in protection in mice immunized with macrophage-processed tumor antigen over control animals. Mineral oil-stimulated macrophages were also capable of processing irradiated EMT6, but macrophages induced by thioglycollate or proteose peptone were not. Freeze-thawed mycobacteria-stimulated macrophages were nearly as effective as viable macrophages in processing tumor antigen, but heat-treated macrophages lost this capacity. The immunity generated was specific and could be passively transferred by immune cells but not by immune serum. The results indicate that incubation of tumor antigen with appropriately activated macrophages leads to the enhanced induction of immunity to the tumor. Macrophage enzymes may degrade tumor antigens to fragments with few antigenic determinants that preferentially induce cell-mediated immunity.

Adenocarcinoma R-3327 of the Copenhagen Rat as a Suitable Model for Immunological Studies of Prostate Cancer

Abstract: Summary An experimental animal model for the study of host-prostatic tumor cell interactions has been described. R-3327, a line of prostatic adenocarcinoma of the Copenhagen rat, has been proven to be immunogenic to its syngeneic host as evidenced by two different in vitro cell-mediated immune assays. Specificity of the responses has been ascertained on the basis of absence of response: ( a ) of nonimmune lymphocytes to the R-3327 tumor antigen(s); ( b ) of R-3327 immune lymphocytes to several normal tissues including normal prostate; ( c ) of immune lymphocytes to unrelated squamous cell prostatic carcinoma of the Copenhagen rat. Furthermore, the presence of tumor has an effect in several nonspecific aspects of host response, inducing splenomegaly, heightened responses to nonspecific mitogens in lymphocyte transformation assay, and increased levels of killer cell action. Since there are many histological, biochemical, and functional analogies between this tumor line and human prostate carcinomas, this system appears to be suitable for immunological and possible immunotherapeutic studies of this type of neoplasia.

Characterization of Effector Lymphocytes Associated with Immunity to Murine Sarcoma Virus (MSV)-Induced Tumors II. Repeated Stimulation and Proliferation In Vitro of Specific Cytolytic T Lymphocytes

Abstract: Cytolytic T lymphocytes (CTL) and specific CTL precursor cells can be generated during the immune response to syngeneic tumors induced by murine sarcoma virus (MSV) in the mouse. MSV-immune spleen cells yield high numbers of specific CTL after incubation in vitro with irradiated tumor cells in syngeneic secondary mixed leukocyte-tumor cell cultures (sec-MLTC). Peak cytolytic activity generated in sec-MLTC is detectable on day 7 after culture initiation and decreases slowly thereafter. This report presents data showing that highly active CTL could be regenerated upon tertiary stimulation of long-term sec-MLTC with irradiated tumor cells bearing MSV-associated antigens. CTL activity recovered from tertiary MLTC could be detected in a short-term (3 hr) 51 Cr release assay, and increased levels of cytolysis were already evident 24 hr after culture re-initiation. It was also shown that cells recovered from MLTC 12 days after tertiary restimulation could be further stimulated by specific tumor antigen in quaternary MLTC to yield increased CTL numbers. These results thus indicated that T lymphocytes could be repeatedly stimulated by specific tumor antigen in syngeneic MLTC to yield increasing numbers of cytolytic cells. Furthermore, the tumor antigen used for the initial stimulation of MSV-immune spleen cells in sec-MLTC appeared to have induced a specific selection of CTL precursor cells, since only syngeneic tumor cells bearing MSV-associated antigens were capable of inducing high levels of CTL regeneration in tertiary MLTC.

Immune RNA-mediated transfer of tumor antigen responsiveness to unresponsive peritoneal exudate cells from tumor-bearing animals.

Abstract: Peritoneal exudate cells (PEC) from mice inoculated 5 to 7 days previously with 1 × 106 MOPC-315 plasmacytoma cells exhibit in vitro migration-inhibitory factor reactivity to soluble tumor-associated antigens. By 10 to 14 days of tumor growth, PEC from MOPC-315-bearing mice did not elicit migration-inhibitory factor when stimulated with MOPC-315 tumor-associated antigens but were still capable of migration-inhibitory factor production when stimulated with nontumor antigens. RNA-rich extracts prepared from 5- and 6-day postgrafting tumor bearers were capable of transferring tumor antigen reactivity to both normal PEC and PEC from unresponsive MOPC-315-bearing mice. On the other hand, RNA from unresponsive tumor bearers was incapable of transferring tumor antigen reactivity to normal mouse cells.

Delayed hypersensitivity in tumor‐bearing mice. In vitro activation of “eclipsed” spleen cells

Abstract: At various stages during the progressive growth of a transplanted sarcoma in BALB/c mice, the delayed hypersensitivity response to tumor antigen was determined using the food-pad swelling test (FPS) and the leukocyte migration inhibition assay (LMI). A close correlation was observed between the in vivo and in vitro assays. "Early" recognition of tumor antigen was detected 24 h after tumor inoculation by both techniques and this positive response was maintained until day 15. As the tumor grew larger, the delayed hypersensitivity response in vivo vanished, while the delayed hypersensitivity response in vitro disappeared about 3 days later. This suppression or "eclipse" of the anti-tumor cellular immune response was specific for the type of tumor used, and could be reversed in vitro by means of a low pH treatment of lymphoid cells.

Reversal of SV40 tumor-mediated suppression of spleen cell cytotoxicity by antibody.

Abstract: Spleen cells obtained from hamsters bearing PARA-7 tumors greater than 1.0 cm were not reactive in microcytotoxicity assays unless preincubated overnight. The events occurring during in vitro incubation which lead to reversal of tumor-mediated suppression of cellular immunity were investigated. After 24 hr of incubation, supernatants overlying spleen cells from tumor-bearing hosts contained a factor which blocked cytotoxicity of simian virus 40 (SV40) 3 -sensitized spleen cells at the PARA-7 target cell level but not at the effector cell level. The preparations did not mediate antibody-dependent cellular cytotoxicity (ADCC). Opposite results were obtained in assays of culture medium overlying spleen cells from hosts with a tumor burden less than 0.1 cm. Although ADCC activity was present, no significant blocking was detectable. Treatment of inactive spleen cells with anti-hamster γ-globulin in the presence of complement (anti-HGG + C) prevented activation and formation of blocking factor but did not impair the cytotoxic activity of already activated cells. Addition of SV40 antiserum to anti-HGG + C-treated cells led to effector cell activation, whereas heterologous virus-immune sera did not. Control studies established that the antibody-mediated recovery of cytotoxicity was not due to arming. Further studies showed that PARA-7 tumor antigen extract blocked at the effector cell level, not at the target cell level. Addition of PARA-7 extract to spleen cell supernatants mediating ADCC resulted in formation of a factor which blocked at the target cell level but not at the effector cell level. These data are compatible with the following interpretation. Spleen cell unresponsiveness is due to antigen blockade. Recovery of cytotoxicity occurs because antibody synthesized during the incubation period promotes elution of antigen from the effector cell surface. Thus, activation is accompanied by the generation of tumor antigen-antibody complexes.

Role of Tumor Antigen in Vaccine Protection in Marek’s Disease

Abstract: Recently, we have observed that chickens vaccinated with the herpesvirus of turkey (HVT) develop lymphoproliferative lesions (1) and a cell mediated immune response to the Marekfs disease tumor associated surface antigen (MATSA) (2). The purpose of this presentation is to consider these observations in view of the overall mechanism of vaccine protection in Marekfs disease (MD) and to speculate on the possible role MATSA immunity may play in protection. Furthermore, additional data are presented that confirm earlier observations on the presence of MATSA in HVT infected chickens.

Immune response of athymic nude mice to papovavirus sv40 tumor-associated antigens.

Abstract: The requirement of T cell functions in the induction of immune response to SV40-specific transplantation rejection antigen and intranuclear tumor antigen was studied using athymic nude mice. The results obtained indicate that virus-immunized athymic nude mice were unable to reject SV40 tumor cell challenge, and sensitized lymphocytes capable of inhibiting tumor growth in vivo could not be demonstrated in the spleens of virus-immunized mice. Athymic nude mice bearing tumor induced by virus-free SV40-transformed BALB/c cells failed to develop antibodies to intranuclear T antigen. Athymic nude mice also failed to respond to viral antigens. Thus it can be concluded that T cell functions are required in the induction of cellular immune response to SV40-specific transplantation rejection antigen and in humoral immune response to SV40-specific T antigen and virion antigen.

Immunogenicity of solubilized tumor antigen extracted from P1798 murine lymphoma cells or isolated from tumor-bearer ascites fluid and reactivity with anti-thy-1.2 antiserum.

Abstract: Solubilized antigen was prepared from P1798 lymphoma cells by sonication, 3 M KCI extraction, or isolated from the ascites fluid of syngeneic tumor-bearing BALB/c mice Antigen was detected and quantitated by its ability to block activity of anti-P1798 serum raised in syngeneic mice, as assayed by cytotoxic and indirect immunofluorescence tests It was established that the reaction was immunologically specific as the P1798 antigen did not inhibit the binding to L1210 lymphoma cells of antisera raised against L1210 in syngeneic DBA/2 or allogeneic BALB/c mice Vaccination of BALB/c mice with different subcellular fractions of sonicated antigen or with ascites fluid resulted in protection against a live P1798 challenge with results comparable to those obtained using iodoacetamide-modified tumor cells Solubilized antigen prepared by each of the three methods eluted from a Bio-Gel A5m agarose column exclusively in an early peak that had a molecular weight estimated to be greater than 2 X 10(6) This column-fractionated antigen was shown to cross-react with antiserum raised against Thy-12 antigen, which is present on P1798 cells The purified P1798 antigen sedimented at 200,000 g and was shown to protect syngeneic mice in immunoprophylactic tests

Lymphokines of T and B Cells

Abstract: Lymphocytes from MC sarcoma-bearing mice were exposed to a soluble tumor antigen. The lymphokine-containing supernatant thus obtained was fractionated on Sephadex G-75. Fractions were tested for their activity to reduce the surface charge of indicator macrophages by cell electrophoresis technique. When un-separated spleen or lymph node cells were used the charge-reducing activity of the supernatant was found in three regions according to molecular weights of about 100,000, 60,000 – 35,000 and 13,000 Daltons. The appearance of activity was found to be time-dependent. As indicated by tests with separated lymphocytes both B and T cells appear to release charge-reducing activity.