Non-viral Origin Research Articles

Suppression of T cell‐mediated immunity by tumor cells: Immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors

In studying the immunogenicity of spleen cells and tumor cells in the generation, of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell-free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus-induced leukemia FBL-3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non-viral origin. The viral component was sensitive to UV-irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non-viral component was UV-resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromicroscopy, and by the virus focus-inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune responses in the tumor-bearing hosts.

Comparative studies of two types of “spontaneous” malignant alteration of ST/A mouse lung fibroblasts propagated in vitro

Two types of apparently spontaneous malignant alterations of fibroblastlike ST/a mouse lung cells (ST-L cells) grown in vitro are described. One type is characterized by a high tumorigenic potential of the altered cells in nonconditioned syngeneic recipients, a fibroblastlike morphology with cell surface showing very few microvilli by scanning electron-microscopy (SEM), and a growth pattern typical of nontransformed cells. These cells were described as R- cells. The other type is characterized bya low tumorigenic potential in non-conditioned, immunocompetent syngeneic recipients, rounding up of the cells which by SEM showed numerous microvilli on the surface, and a growth pattern typical of transformed cells. These cells were described as round cells or R+ cells. In immunoincompetent mice, R+ cells readily produced sarcomas, which grew faster than those produced by R- cells. Both types of ST-L cells expressed murine leukemia virus (MuLV) when tested in a peroxidase anti-p30 plaque test. The concentration of murine leukemia virus envelope glycoprotein (gp70) has previously (5) been shown to be threefold higher in R+ cells compared to R- cells. Furthermore, round-cell transformation was accompanied by the development of crossreacting rejection antigens protective against a secondary shallenge with Ehrlich ascites tumor and with syngeneic dimethylbenzanthracene induced ST/a mouse leukemia (STABAL). A similar protection was obtained by preimmunization with a cloned embryonic feral mouse cell line (SC-1) infected with ST-L virus as well as with virus-free SC-1 cells, suggesting the presence of rejection antigens both of viral (gp70) and nonviral origin.

Interferons: Rationale for Clinical Trials in Neoplastic Disease

Interferons, cell glycoproteins synthesized in response to viral infections and various nonviral inducers, have proved therapeutically effective for viral infections in experimental models and in humans. Current evidence suggests interferons may also prove effective as antitumor agents in humans. Potent effects on cellular function result from interferons. Cell surface structure and enzyme levels are altered. Immunologic responses thought to be important in tumor immunity are augmented. Interferons have antiproliferative effects on the replication of normal and neoplastic cells. Interferons are effective in animals against tumors of both viral and nonviral origin. Clinical trials in cancer have been limited by the availability and cost of human interferons. However, results in small numbers of patients have been encouraging. This paper review experimental and clinical findings regarding the rationale for use of interferons in neoplastic disease.

Serological detection of a polyoma-tumor-associated membrane antigen.

Syngeneic antisera raised against three polyoma tumors, SEYF-a SESO and SEWE, of strain ABY, A and ASW origin, respectively, contain antibodies directed against multiple specificities. One specificity is cross-reactive for the three polyoma tumors, but appears to be absent from a large variety of other tumors tested. Other, more "public" antigens are shared with a variety of other tumors of viral or non-viral origin. Five different public specificities of this type have been demonstrated and to some extent defined. Since the SEWE ascites tumor, with the shortest passage history, is much less liable to induce antibodies against the public specificities than the long-passaged SEYF-a and SESO, it is likely that the corresponding antigenic determinants arise as a result of passenger virus pick-up during continued passage, or are due to secondary cytogenetic changes.

Inhibition by interferon preparations of a solid malignant tumour and pulmonary metastasis in mice.

WE have reported the efficacy of exogenous interferon preparations in inhibiting the development of several virus-induced leukaemias of mice. These are the Friend1,2 and Rauscher leukaemias3 as well as the spontaneously appearing lymphoid leukaemia of AKR mice4. Comparable interferon preparations also inhibited the growth of transplantable ascitic tumours (of viral and non-viral origin) and markedly increased the survival of tumour inoculated mice5,6. We thought it would be interesting to determine the effect of interferon on the growth of a solid metastasizing tumour.