Showing papers on "Tumor antigen published in 1978"

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.

Regulation of the Immune Response to Tumor Antigen IV. Tumor Antigen-Specific Suppressor Factor(s) Bear I-J Determinants and Induce Suppressor T Cells in Vivo

Abstract: The administration of crude suppressor factor(s) to normal animals for 4 days resulted in the development of a population of suppressor cells that act in a manner analogous to the suppressor cell population used for production of factor. These factor-induced suppressor cells are T cells and exhibit an antigen specificity similar to that displayed by the tumor-induced suppressor cells. Thus, tumor-specific suppressor factor(s) bear I-J determinants and are capable of inducing the appearance of suppressor T cells in the nontumor-bearing host, which may then act in a specific manner to limit host responsiveness to tumor antigen.

Evidence that tumor antigens enhance tumor growth in vivo by interacting with a radiosensitive (suppressor?) cell population

Abstract: The growth of a small number of cells from each of two chemically induced BALB/c sarcomas was enhanced when x-irradiated (15,000 rads) cells of the same sarcoma were mixed with the tumor inoculum This enhancement did not occur if the recipients had been given a total body x-irradiation of 450 rads Tumor neutralization (Winn) tests showed that tumor cells irradiated in vitro enhanced tumor growth only in the presence of radiosensitive cells present in the spleens of both nonimmune and tumor-bearing mice On the basis of these findings we postulate that tumor antigen blocks effective tumor immunity by a mechanism that involves a suppressor cell population

Abelson antigen: a viral tumor antigen that is also a differentiation antigen of BALB/c mice.

Abstract: We report here the serologic detection of a cell surface antigen common to cells transformed by the Abelson murine leukemia virus (A-MuLV) and to normal hematopoietic cells from certain strains of mice. Serum from C57BL/6 mice hyperimmunized with syngeneic A-MuLV lymphoma cells was cytotoxic for the immunizing cells; this reaction was used as the serologic test system for recognition of A-MuLV antigens. Absorption analysis using 40 tumors and 21 cell lines revealed that two serologic specificities were detected by this test system: (i) FMR antigen(s) related to the Moloney MuLV helper (the virus from which A-MuLV was originally derived), and (ii) an antigen expressed on all cells transformed by A-MuLV. The A-MuLV-specific antigen was also present on uninfected cells from BALB/c bone marrow, spleen, and fetal liver but not from adult liver, thymus, lymph nodes, or peripheral blood. Abelson antigen was not expressed on bone marrow or spleen cells of 12 other mouse strains. In light of the original isolation of A-MuLV from a BALB/c mouse infected with Moloney virus, it is possible that Abelson antigen is a serologic marker for a gene of BALB/c mice, normally encoding a cell surface molecule, that was incorporated into the Moloney virus genome during the generation of A-MuLV.

Common methionine-tryptic peptides near the amino-terminal end of primate papovavirus tumor antigens.

Abstract: The tumor antigens directed by human papovaviruses BK and JC and the monkey papovavirus simian virus 40 have two methionine-containing tryptic peptides in common. These peptides are constituents of the small forms of papovavirus tumor antigen (17,000 daltons) which are present in lytically infected and transformed cells and which are believed to share some amino acid sequences with the amino-terminal portion of the larger tumor antigen species (97,000 daltons). In addition to the two peptides, which are present in all three papovavirus tumor antigens, the larger forms of the tumor antigens specified by simian virus 40 and BK virus share four other methionine-containing tryptic peptides, two of which are also present in the smaller (17,000 daltons) species of antigen. The occurrence of common peptides at the amino-terminal portion of tumor antigens of primate papovaviruses suggests that these conserved regions may play a fundamental role in the function of these proteins and in the propagation of these viruses in nature. The tryptic peptides of the small forms of papovavirus tumor antigen were examined and compared to those present in the large species. Out of a total of nine and ten methionine-containing peptides in the 17,000-dalton tumor antigens of simian virus 40 and BK virus, seven and nine peptides, respectively, are constituents of the corresponding larger (97,000 daltons) forms of the antigen.

DNAs of simian virus 40 and polyoma direct the synthesis of viral tumor antigens and capsid proteins in Xenopus oocytes.

Abstract: Purified simian virus 40 and polyoma DNAs injected into nuclei of Xenopus oocytes were transcribed and subsequently translated into virus-specific tumor antigens and capsid proteins. Simian virus 40 large and small tumor antigens synthesized in the oocytes were indistinguishable, by gel electrophoresis and [35S]methionine-labeled tryptic peptide mapping, from the corresponding polypeptides synthesized in CV-1 African green monkey cells. The synthesis of large simian virus 40 tumor antigen implies the correct splicing of its mRNA, which is complementary to nonadjacent nucleotide sequences in the early region of the viral genome. Polyoma DNA directed synthesis of two polyoma tumor antigen polypeptides, 57,000 Mr and small tumor antigen, and of the main capsid protein.

Regulation of the Immune Response to Tumor Antigen: VI. Differential Specificities of Suppressor T Cells or Their Products and Effector T Cells

Abstract: Suppressor T cells arising during the development of certain murine methylcholanthrene-induced fibrosarcomas have previously been shown capable of limiting only those effector responses generated against the homologous tumor. Thus, S1509a-induced suppressor T cells inhibit immune reactivity only to the S1509a tumor in S1509a immune mice and have no effect on the rejection of SAI tumors in SAI-immune animals. In contrast to this is the cross-reactivity of effector cells in this system, whereby animals rendered immune to either the S1509a or SAI sarcoma are equally capable of rejecting a challenge of the opposite tumor. The specificity of suppression has been further defined in the present study, which demonstrates that S1509a-induced suppressor cells can inhibit responsiveness only to the S1509a sarcoma, even in the simultaneous presence of both the S1509a and SAI tumors. Furthermore, the suppressor factor that is obtainable from suppressor T cells demonstrates a similar precise specificity in its ability to limit selectively reactivity only against the inducing tumor, regardless of the simultaneous expression of antigens on other tumors recognized by cross-reactive effector cells. These results suggest that the antigenic determinants recognized by effector and suppressor T cells are different, and may provide a model for further dissection of suppressor cell function in vivo.

Somatic cell hybrids producing antibodies specific for the tumor antigen of simian virus 40

Abstract: We have produced somatic cell hybrids between mouse myeloma cells deficient in hypoxanthine phosphoribosyltransferase IMP: pyrophosphate phosphoribosyltransferase; EC 2.4.2.8) and spleen cells derived from mice primed with either syngeneic or allogeneic cells transformed by simian virus 40. Such hybrids produced antibodies specific for simian virus 40 tumor (T) antigen. Only four of twelve independent hybrid cell cultures produced antibodies against simian virus 40 T antigen that crossreacted with the T antigen induced by BK virus, a human papovavirus isolated from patients who had undergone immunosuppressive therapy.

Failure to demonstrate papovavirus tumor antigen in human cerebral neoplasms

Abstract: Cell cultures derived from 80 brain tumors failed to show the intranuclear tumor (T) antigen common to cells transformed by simian virus 40 (SV40) or BK or JC viruses.

Development and persistence of cytolytic T lymphocytes in regressing or progressing Moloney sarcomas.

Abstract: Intratumoral T lymphocytes were recovered sequentially after induction of regressing or progressing Moloney sarcomas in BALB/c mice and were assayed quantitatively for their ability to kill specifically the tumor (MSC) cells used for induction. The cytolytic activities of the two lymphocyte populations described two distinct biphasic kinetic profiles that were similar in amplitude and duration but separated from each other by 4-6 days. In progressing neoplasm, there was a rapidly occuring accumulation of T lymphocytes highly cytolytic for MSC cells. This response, however, was not sustained and disappeared in association with the onset of unchecked tumor growth. In contrast, T lymphocyte cytolytic activity developed more slowly in regressing sarcomas and attained peak levels coincident with the beginning of tumor regression. Similar changes in cytolytic activity characterized T lymphocytes in lymph nodes draining tumors. When cultured in vitro for 4 days, non-cytotoxic T lymphocytes from regional lymph nodes draining progressing sarcomas regained very high levels of cytolytic activity. Such restitution was diminished, however, if MSC cell lysates, macrophages or macrophages fed MSC cell lysates were present during the culture period. These experiments provided presumptive evidence that T lymphocyte-mediated cytolytic activity was lost in progressively growing Moloney sarcomas as a consequence of suppression in vivo of the genesis and/or functional expression of cytolytic T lymphocytes, perhaps by macrophages and/or soluble tumor antigen.

Soluble Suppressor Factor from the Spleens of Tumor-bearing Mice

Abstract: Spleen cells from tumor-bearing mice when cultured for 3 to 5 days released a soluble factor into the media that suppressed the stimulation of lymph node and spleen cells by tumor antigen or mitogens. Spleens from mice bearing MC43 tumors for 14 days were capable of producing suppressor factor in vitro , while those from mice bearing the tumor for 10 days or less failed to do so. Lymph node cells from the same animals did not produce suppressor factor in vitro . The suppressor factor was produced by a nonadherent cell population, was heat stable, was lost on dialysis, and did not appear to be tumor antigen or thymidine.

Changes in tumor immunity during therapy determined by leukocyte adherence inhibition and dermal testing.

Abstract: Leukocyte adherence inhibition (LAI) is an easily carried out in vitro test for tumor reactivity which is based on the prevention of adherence of leukocytes incubated with antigen to which the donor is immune. In this study a comparison is made with dermal response to tumor antigen. A total of 234 patients were tested, 74 of whom had melanoma, 111 of whom had squamous cell carcinoma of the head and neck, 18 of whom had neuroblastoma and 31 of whom had other tumors. Forty-two persons without tumors acted as controls for the LAI test. A high degree of correlation was found between LAI and dermal response. Furthermore, LAI exhibited marked tumor specificity and showed a ten-fold greater sensitivity than dermal response. LAI may be used to monitor serial changes in tumor reactivity in cancer patients.

Glycolipid compositions for transplanted tumor immunotherapy

Abstract: A composition which is capable of specifically inducing an immunity when administered into the body of a host in association with a tumor antigen, or which is capable of non-specifically enhancing an immunizing function when administered into the body of a tumor-carrying host, comprising a glycolipid as active ingredient in association with a pharmaceutically acceptable carrier, wherein the saccharide moiety of the glycolipid is selected from the group consisting of fructose, glucose and sucrose.

Demonstration of specific cell-mediated anti-tumor immunity in lung cancer to autologous tissue extracts.

Abstract: Cell-mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 microliter) lymphocyte proliferation (LP) assay. Positive lymphoproleferative responses were observed with cryopreserved intact mitomycin-C-treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 microgram or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti-tumor immunity.

Immune Response to a Mammary Adenocarcinoma V. Sera from Tumor-Bearing Rats Contain Multiple Factors Blocking Cell-Mediated Cytotoxicity

Abstract: Sera from Fischer rats 3 to 13 days after i.p. injection of syngeneic 13762A mammary adenocarcinoma contain three factors specifically blocking cell-mediated cytotoxicity (CMC). The major blocking factor is a 160,000-dalton IgG that combines specifically to cytolytic lymphocytes but not to tumor cells or tumor antigen, and that is not dissociated after treatment with 8 M urea. The other factors have been putatively identified as tumor antigen ( 200,000 daltons). Injecting the tumor antigen into tumor-free rats induced spleen cells specifically cytotoxic to the 13762A tumor and provided partial protection to challenge with live tumor cells. Treating soluble antigen-antibody complexes with 8 M urea decreased the size of the blocking activity from greater than 200,000 to less than 70,000 daltons. Although the IgG fraction dissociated from the complex did not block CMC, it did recombine with the tumor antigen fraction to transfer activity to the >200,000-dalton fraction. In contrast, mixing tumor antigen with the IgG fraction that did block CMC did not alter the size of the blocking activities.

Murine Rous-sarcoma-specific immunity detected by leukocyte adherence inhibition: inhibitory effect of normal serum.

Abstract: The standard one-stage lymphocyte adherence inhibition (LAI) assay was used to investigate cellular and humoral immune responses within the murine Rous sarcoma system. Significant specific cellular reactivity to Rous sarcoma antigen extracts was detected when the responder peritoneal exudate cells (PEC) were obtained from mice bearing or immunized against primary or transplanted Rous sarcomas; no cellular reactivity to control methylcholanthrene (MC)-induced tumor antigen extracts was observed. Similarly, specific cell-mediated recognition of MC tumor antigen extract was demonstrated. Initial experiments designed to assess the role of serum components in the LAI assay demonstrated that normal mouse serum of C57BL/10ScSn, B10.D2, or A/WySn origin, either fresh or frozen, obtained from old (over 7 months) or young (under 6 weeks) mice non-specifically abrogated the specific loss of PEC adherence.

Tumor immunity to murine plasma cell tumors. V. Demonstration of a unique tumor antigen that is not associated with the myeloma idiotype.

Abstract: A plasma‐cell tumor, Cl.18 of C3H/He derivation, exhibits a unique tumor‐associated antigen (TAA) which is detectable both in vitro and also as a tumor‐associated transplantation antigen (TATA) in vivo. Immunoglobulin idiotypic determinants have been thought to be prominent TATAs. Studies were performed to determine whether the unique TAA of Cl. 18 is its immunoglobulin idiotypic determinant. Mice immunized with CI. 18 myeloma protein (CI.18 MP) exhibit some protection to subsequent challenge with Cl. 18 tumor cells indicating that the CI.18 idiotypic determinant can indeed act as a weak TATA. However, in vitro lysis of CI. 18 tumor cells by cytotoxic T cells induced in vitro to CI. 18‐unique TAA is not blocked by CI. 18 MP, either in soluble form or when bound to sheep red blood cells. Spleen cells from mice immunized to CI. 18 MP in vivo do not undergo a secondary cytotoxic response when stimulated in vitro by CI.18 tumor cells. When C3H mice are immunized with tumor cells they are highly resistant to a subsequent challenge with CI. 18 tumor cells, and spleen cells from these mice show a marked secondary cytotoxic response when stimulated in vitro by CI. 18 tumor cells. Spleen cells from these mice, however, do not mount a secondary cytotoxic response when stimulated with CI.18 MP in vitro. We conclude that the unique TAA present on CI.18 cells is not the idiotypic immunoglobulin determinant, although both antigens can act as TATA in vivo. These studies support the view that although some plasmacytomas may express cell surface immunoglobulin idiotypic antigens, these are not the major surface antigens that act as tumor‐associated antigens.

Leukocyte migration inhibition of tumor antigen and purified protein derivative reactivity in guinea pigs sensitized to line 10 hepatocarcinoma and BCG.

Abstract: Agarose microdroplet leukocyte migration inhibition (LMI) assays were performed to measure reactivity against line 10 hepatocarcinoma antigens and purified protein derivative (PPD) with the use of peripheral blood leukocytes from line 10 and/or BCG-sensitized syngeneic guinea pigs. The assay was quite sensitive and detected leukocyte migration inhibition with concentrations as low as 12.6 ng protein/ml of the crude sonicate of the line 10 tumor and 0.1 pg PPD. Specificity was shown by lack of reactivity in leukocytes of line 10 and/or BCG-sensitized animals with antigen preparations of L2C leukemia cells or normal syngeneic liver. Furthermore, leukocytes from normal control guinea pigs failed to react with any antigen. The results also suggested antigen cross-reactivity between line 10 tumor and BCG. Leukocytes from guinea pigs sensitized to only BCG became LMI reactive to the line 10 sonicate as well as PPD. No reactivity was observed with leukocytes of the animals in simultaneous tests with a sonicate of guinea pig L2C leukemia cells. The results demonstrated the usefulness of this microassay in detection of LMI reactivity with low antigen concentrations and small volumes of whole blood.

Influence of surgery, irradiation, chemotherapy, and immunotherapy on growth of a metastasizing rat mammary adenocarcinoma.

Abstract: Based upon the hypothesis that a factor most pertinent to the absence of an effective immune response in cancer is the inadequacy of the antigenic stimulus provided by the neoplasm, either in terms of weak immunogenicity of the tumor antigen or of the necessary antigen mass available to the reticuloendothelial tissues at any one time for effective sensitization, the host immune response capabilities were stimulated within a time frame synchronous with a greater release of tumor antigens. In the treatment of a metastasizing, solid tumor model syngeneic with F344 rats, immunotherapy was most effectively applied in combinations with chemotherapy and/or localized radiotherapy, therapeutic modalities that induced a degree of oncolysis and tumor resorption. Surgery combined with chemotherapy permitted evaluation of therapeutic effects against metastases. The methanol-soluble fraction of Mycobacterium butyricum was used as the nonspecific immunologic adjuvant.

Immunity Against MOPC 104E Plasmacytoma: Effects of Tumor Size and Time Post Therapy on In Vivo Tumor Immunity

Abstract: BALB/c mice with the plasmacytoma MOPC 104E were cured of palpable tumors (6-15x10(7) cells) with a single injection of cyclophosphamide (10 mg/kg). Animals cured of tumor showed a considerable increase in their ability to reject secondary challenge with graded numbers of viable tumor cells. Mice with palpable subcutaneous tumors were cured therapeutically and rechallenged 22, 44, or 120 days post therapy. The ability of such animals to reject secondary tumor cell challenge was similar in all groups, which implied that in vivo tumor immunity remained relatively constant for at least 4 months post therapy. A second group of animals was treated therapeutically (10 mg cyclophosphamide/kg) 4, 11, or 20 days post tumor cell injection. These therapeutically treated animals were then rechallenged with various numbers of viable tumor cells 30 days post therapy. Mice given cyclophosphamide 4, 11, or 20 days post tumor injection rejected 6, 60, or 400 times as many tumor cells, respectively, as did control animals. These results implied that, over the range of tumor sizes investigated, exposure to greater amounts of tumor antigen resulted in increasing amounts of residual tumor immunity following cure.

Delayed hypersensitivity reactions in patients with breast cancer.

Abstract: Fifty six patients with metastatic cancer of the breast (stage IV) were treated with Cyclophosphamide, 5-Fluorouracil and Cyclophosphamide + 5-Fluorouracil. Tests for delayed hypersensitivity to homologous tumor antigen before treatment were positive in 83.9% and negative in 16.1%. Response to DNCB was positive before treatment in 51.8% and negative in 48.2%. Following chemotherapy the skin reaction, to homologous tumor antigen remained positive, only in 12.6% and negative in 87.4%. The reaction of DNCB remained positive after treatment only in 17.8%. In the remaining 82.2% suppression of the reaction occurred. These data show that chemotherapy may suppress, to a certain excent, immune responses. It is established that among patients who have shown a positive reaction to homologous tumor antigen 55.3% of all cases have displayed objective response to the treatment, and among these with negative skin reactions objective responses were observed in 22.22% of all cases. In patients with positive DNCB reactions objective responses were observed in 79.3% and among the negative ones--in 37.4%.

Progression of the immune response to solubilized tumor antigens.

Abstract: Local adoptive transfer assays (LATA) were used to analyze and compare the progression of the immune response in C3H/HeJ mice to irradiated tumor cell vaccine and to crude 3M KCl solubilized antigens extracted from a syngeneic methylcholanthrene-induced fibrosarcoma. Sequential LATA performed 2, 6, 9, 12 and 15 days after soluble antigen pretreatment of spleen cell donors revealed a sinusoidal evolution of lymphoid cell activity. An initial brief period of potent tumor facilitation (days 6–9) was followed by a phase of tumor neutralization (days 9–12) which decayed by day 15. On the other hand, spleen cells from donors sensitized with irradiated tumor cells exhibited consistent tumor neutralization which was sustained throughout 15 days. Thus the tumor growth facilitation observed only in CSA-treated donors may represent a qualitative difference in the immune state induced by soluble, as opposed to cellular, forms of tumor antigen.

Inhibition of leukocyte migration by tumor-associated antigen and its modification by serum; IgA as a blocking factor.

Abstract: Based on the investigations of patients the migration inhibition assay proved to be a useful method for the detection of antitumorous cellular immunity. Out of the twenty patients tested 15 gave migratory inhibitory effect against specific tumor antigen. In 8 cases out of the above 15 the blocking activity of sera has been proved. This blocking activity is bound to IgA subclass. The complement played an "unblocking" role. The modifying role of serum factors in cellular immunity against tumors was discussed.

The Effect of Anti-Ia Alloantisera on Syngeneic Tumor Immunity

Abstract: Tumor specific suppressor T cells (STC) arise in A/J mice as a consequence of inoculation of syngeneic methylcholanthrene induced fibrosarcomas, S1509a and SAI, and elaborate tumor antigen specific suppressor factor(s) (SF). SF which bears determinants encoded by the K end of the H-2 MHC, and STC which express I-J subregion encoded cell surface determinants dampen the primary response and limit the secondary effector reactivity to tumor in vivo. Daily treatment of normal A/J mice with 2 µl of (DBA/2 × 3R)F1 anti-5R (anti-I-J) antisera beginning at the time of a 106 S1509a tumor inocula resulted in a highly significant reduced tumor growth and an abrogation of the capacity of such mice to adoptively transfer suppression. Furthermore, anti-I-J antisera could also limit tumor incidence and appearance when used with smaller tumor inocula. The sera effect was specific and was lost only after absorption with lymphoid cells of the appropriate haplotype.

Tumor immunity following cryosurgery or electrocauterization.

Abstract: Cryosurgery of MCA-10 in C57BL mice resulted in significantly greater humoral and lymphocyte-mediated cytotoxicity to MCA-10 target cells than in untreated, tumor-bearing mice or animals which had undergone tumor amputation. This result was tumor specific and could be reproduced by treatment of the tumor-bearing and amputated mice with frozen exogenous tumor antigen. A similar response was produced by electrocauterization of tumor.