Serum mediated inhibition of cellular immunity to methylcholanthrene-induced murine sarcomas.
TL;DR: Serum from the tumor-bearing animals, obtained at the time of tumor removal and explantation into culture, abrogated the inhibitory effect of autochthonous lymph node cells (LNC), and serum taken before palpable tumors could be detected did not abrogate the inhibitedory LNC effect.
About: This article is published in Cellular Immunology.The article was published on 1970-05-01. It has received 187 citations till now. The article focuses on the topics: Cellular immunity & Methylcholanthrene.
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TL;DR: Evidence indicating antigenic cross‐reactivity between tumors of the same histological type was obtained for the following seven groups of neoplasms: malignant melanomas, carcinomas of the colon, breast, testis, endometrium and ovary, and various sarcomas.
Abstract: Peripheral blood lymphocytes from a total of 373 tumor patients were tested by either a colony inhibition or a cytotoxicity test for cell-mediated immunity against human neoplasms of various histological types. Lymphocytes from 51 of 59 patients studied (88%) either reduced colony numbers formed by plated autochthonous tumor cells or were cytotoxic to them, and lymphocytes from 78 of 87 patients tested (89%) had a similar effect on allogeneic tumor cells of the same histological type as those of the lymphocyte donors. Evidence indicating antigenic cross-reactivity between tumors of the same histological type was obtained for the following seven groups of neoplasms: malignant melanomas, carcinomas of the colon, breast, testis, endometrium and ovary, and various sarcomas. Lymphocytes affecting tumor cells had no effect on normal cells from the same patient, or on cells from other types of neoplasms than the target cells under study.
The degree of cell-mediated immunity, as detectable with the techniques employed, was approximately the same in patients having active neoplastic disease as in patients who were clinically symptom-free. Eleven of 12 patients who were tested after having been symptom-free for more than 2 years had a lymphocyte-mediated anti-tumor immunity.
Mise en Evidence D'une Immunite A Mediation Cellulaire Envers les Neoplasmes Humains de Divers Types Histologiques
Nous avons etudie des lymphocytes du sang peripherique de 373 cancereux au moyen de tests d'inhibition des colonies et de cytotoxicite en vue de mettre en evidence une immunite a mediation cellulaire envers les neoplasmes humains de divers types histologiques. Les lymphocytes de 51 des 59 sujets etudies (88%) ont fait diminuer le nombre de colonies formees par les cellules tumorales autochtones ou se sont montres cytotoxiques a l'egard de ces cellules; les lymphocytes de 78 des 87 sujets testes (89%) ont eu un effet analogue sur les cellules tumorales allogeneiques du měme type histologique que celles des donneurs de lymphocytes. Nous avons obtenu la preuve de l'existence d'une reactivite antigenique croisee entre les tumeurs du měme type histologique pour les 7 groupes de neoplasmes suivants: melanomes malins, epitheliomas du colon, du sein, des testicules, de l'endometre et des ovaires, et divers sarcomes. Les lymphocytes agissant sur les cellules tumorales n'ont pas eu d'effet sur les cellules normales du měme malade, ni sur les cellules de neoplasmes de types histologiques differents.
Le degre d'immunite a mediation cellulaire decele au moyen des techniques utilisees etait a peu pres le meme chez les malades atteints d'une neoplasie active que chez les sujets ne presentant aucun symptǒme clinique. Nous avons observe une immunite antitumorale a mediation lymphocytaire chez 11 des 12 malades qui ont ete testes apres ětre restes asymptomatiques pendant plus de deux ans.
673 citations
TL;DR: The studies reviewed in the chapter have given a relatively large amount of evidence for various cell-mediated and humoral immunological reactions against growing tumors, and at least some of the reactions observed in vitro appear to be able to influence tumor growth in vivo.
Abstract: Publisher Summary This chapter reviews the evidence for cell-mediated immune reactions against tumors in animals and man, particularly, the reactions that can lead to destruction of neoplastic cells cultivated in vitro. Various mechanisms by which tumor cells can escape from immunological destruction have been discussed, most notably one involving blocking factors, present in the serum. Findings analogous to those obtained when studying tumor immunity (coexistence of cell-mediated reactivity and blocking serum activity) have been summarized from three other areas (pregnancy, allografting, and chimeras). The studies reviewed in the chapter have given a relatively large amount of evidence for various cell-mediated and humoral immunological reactions against growing tumors, and at least some of the reactions observed in vitro appear to be able to influence tumor growth in vivo .
637 citations
TL;DR: In light of recent studies demonstrating both immunologically aggressive lymphocytes and the presence of blocking antibodies in the blood of neuroblastoma patients, a major role for immunity in ontogenesis seems almost certain.
Abstract: The incidence of malignancy in patients with primary immunodeficiencies is roughly 10,000 times that of the general age-matched population. It is apparent from this review of the literature that each type of immunodeficiency has a distinctive constellation of malignancies associated with it. In light of recent studies demonstrating both immunologically aggressive lymphocytes and the presence of blocking antibodies in the blood of neuroblastoma patients, a major role for immunity in ontogenesis seems almost certain. The role of such antibodies in the formation of lymphoid malignancies, such as occur so frequently in patients with immunologic deficiencies who often do not produce antibodies of any type well, remains unclear.
610 citations
Journal Article•
TL;DR: Preliminary evidence for the lack of clinical toxicity of a monoclonal antibody is provided and circulating blocking antigens as a significant obstacle to serotherapy are identified.
Abstract: A preliminary serotherapeutic trial was undertaken with a monoclonal antibody designated antibody 89 (Ab 89) directed against a lymphoma-associated antigen. In vitro studies demonstrated that Ab 89 could mediate complement-dependent lysis and macrophage adherence but not antibody-dependent cell-mediated cytotoxicity. To evaluate toxicity and therapeutic efficacy, two courses of Ab 89 were administered to a patient with an Ab 89-reactive tumor. Transient decreases in the number of circulating tumor cells and the appearance of circulating dead cells were noted with the infusion of Ab 89. Following administration of 150 mg or more of Ab 89, small amounts of antibody could be demonstrated on circulating tumor cells at a time when no free antibody was found in the serum. The inability to deliver a significant amount of Ab 89 to tumor cells in vivo is thought to be secondary to a circulating tumor antigen. Following each infusion, the amount of this blocking antigen decreased but could not be entirely cleared from the serum. This study provides preliminary evidence for the lack of clinical toxicity of a monoclonal antibody and identifies circulating blocking antigens as a significant obstacle to serotherapy.
415 citations
Cites background from "Serum mediated inhibition of cellul..."
...In animal tumor models, several blocking factors have been extensively studied (15, 16 , 20, 40) and, in humans, prelimi narydescriptionsof blockingfactorshavebeenreported(13,...
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1,248 citations
TL;DR: The demonstration of cellular immunity to TSTA implies that autochthonous neoplasms appear in the presence of immune lymph node cells, which can destroy their cells at least in vitro .
Abstract: Publisher Summary This chapter summarizes the evidence that tumors possess tumor-specific transplantation antigens (TSTA). Virtually all animal neoplasms contain TSTA. Immune reactions against the specific antigens of syngeneic tumors are similar to allograft reactions by which transplanted normal and tumor cells are rejected if they contain isoantigens that are foreign to the recipients. They are to a large extent mediated by immunologically competent cells—that is, lymphocytes and macrophages. The chapter describes several techniques by which cellular immunity to transplantation antigens can be demonstrated, along with a review of different systems in which such techniques were used to detect lymphocyte-mediated immune reactions to TSTA. TSTA are macromolecules present in tumor cells and absent in the normal cells of the same individual and against which immune reactions can be demonstrated with transplantation techniques. The transplantation methods used to demonstrate TSTA can involve the immunization of recipient animals with tumor cells that have been rendered incapable of multiplication (X-irradiation) or that are inoculated in subthreshold doses. Immunization can be also achieved by the inoculation of living tumor cells and excision of the subsequent tumor nodule. The possible role of cellular immunity to TSTA is also discussed in the chapter. The demonstration of cellular immunity to TSTA implies that autochthonous neoplasms appear in the presence of immune lymph node cells, which can destroy their cells at least in vitro . The chapter reviews the phenomenon of allogeneic inhibition. This phenomenon has been postulated to operate in parallel to the immunological mechanisms as part of the organism's defense against antigenic neoplastic cells.
449 citations
TL;DR: MOST experimentally induced animal neoplasms contain tumour specific transplantation antigens (TSTA), against which immunological reactions can be detected both in vivo and in vitro.
Abstract: MOST experimentally induced animal neoplasms contain tumour specific transplantation antigens (TSTA), against which immunological reactions can be detected both in vivo and in vitro1–5.
366 citations
TL;DR: A colony‐inhibition technique was used to demonstrate lymph‐node cell (LNC) mediated immune reactions against tumor‐specific transplantation antigens of primary, Moloney sarcoma virus induced mouse sarcomas.
Abstract: A colony-inhibition technique was used to demonstrate lymph-node cell (LNC) mediated immune reactions against tumor-specific transplantation antigens of primary, Moloney sarcoma virus induced mouse sarcomas. Lymph-node cells from mice in which Moloney sarcomas had regressed spontaneously (regressors), as well as LNC from mice carrying progressively growing tumors (progressors), induced by virus inoculation at an age of 14 days or older, reduced the plating efficiency of Moloney sarcoma target cells.
Serum from mice with progressively growing Moloney sarcomas, but not from mice with spontaneous mammary carcinomas or methylcholanthrene-induced sarcomas, abrogated the inhibitory effect of regressor LNC on Moloney sarcoma cells. Additional evidence for the specificity of the serum effect was obtained in experiments showing that the protective effect of progressor sera could be specifically removed by absorption with Moloney sarcoma cells. Regressor sera gave no protection against target cell inhibition by regressor LNC. It is suggested that progressor sera contain antibodies which mediate an efferent form of immunological enhancement.
Inhibition Serique de l'Immunite a la Tumeur de Moloney
On a utilse une technique d'inhibition des colonies pour mettre en evidence les reactions immunitaires des cellules des ganglions lymphatiques (CGL) contre les antigenes spcifiques de transplnatation de sarcomes primitifs de souris provoques par le virus du sarcome de Moloney. Les CGL des souris chez lesquelles le sarcome de Moloney avait spontanement regresse (“regresseurs”) et les CGL des souris porteuses de tumeurs a croissance progressive (“progresseurs”) induites par inoculation de virus a l'ǎge de 14 jours ou plus ont abaisse la vitalite des colonies de cellulescibles du sarcome de Moloney.
Du serum de souris presentatnt des sarcomes de Moloney croissant progressivement — a la difference du serum de souris atteintes d'epitheliomas mammaires spontanes ou de sarcomes provoques par le methylcholanthrene — a supprime l'effet inhibiteur des CGL “regesseurs” sur les cellules du sarcome de Moloney. On a obteny une preuve supplementaire de la specificite de l'effet du serum par des experiences montrant que l'effet du serum par des experiences montrant que l'effet protecteur des serums “progresseurs” pouvait ětre specifiquement supprime par absorption au moyen de cellules du sarcome de Moloney. Les serums “regresseurs” n'ont donne aucune protection contre l'inhibition des cellules-cibles par les CGL “regresseurs”. On peut avancer l'hypothese que les srums “progresseurs” contiennent des anticorps (ou des fragments d'anticorps) mediateurs d'une forme efferente de facilitation immunologique ou eventuellement de modulation antigenique.
312 citations
TL;DR: A microassay in disposable tissue culture plates was used to demonstrate a cell‐mediated immune response against human urinary bladder carcinoma and no significant cytotoxic effects were produced by control leukocyte suspensions from a patient with prostatic carcinoma, from patients with non‐neoplastic diseases or from normal healthy individuals.
Abstract: A microassay in disposable tissue culture plates was used to demonstrate a cell-mediated immune response against human urinary bladder carcinoma. Leukocytes isolated from peripheral blood of patients with urinary bladder tumours were allowed to react in vitro with cells of bladder tumours, or with a control tumour or normal cells. Both autochthonous and allogeneic leukocytes from patients with bladder tumours strongly reduced the number of plated bladder tumour cells as compared to control leukocytes, but did not affect control tumour or normal cells. No significant cytotoxic effects were produced by control leukocyte suspensions from a patient with prostatic carcinoma, from patients with non-neoplastic diseases or from normal healthy individuals.
The results indicate that human urinary bladder tumours possess tumour-specific antigens which cross-react with each other.
194 citations