Cross‐reactions between tumor cells and allogeneic normal tissues. inhibition of a syngeneic lymphoma outgrowth in h‐2 and non‐h‐2 alloimmune balb/c mice

Abstract

To test whether alloimmunization with H-2 or/and non-H-2 different normal tissues may increase the immunity to syngeneic tumors, groups of BALB/c (H-2d) mice were immunized with a series of allogeneic lymphoid cells and then challenged i.p. with syngeneic lymphoma cells. The outgrowth of otherwise lethal doses of the Moloney virus-induced lymphoma YC8 and of its clones was inhibited in BALB/c mice immune to DBA/2 (H-2d), C3Hf (H-2k), C3H.SW (H-2b), C3H.OH (H-2o2) and to B10 background tissues but not in mice immunized to A/He, BALB.K (H-2k) or BALB.B (H-2b) normal tissues. Anti-YC8 effect was also induced by immunizing BALB/c recipients with a pool of five different allogeneic cell lines which included C3Hf, C57BL/6J (H-2b), N:NIH (H-2q), B10.M (H-2f), and DBA/2 lymphoid cells. No growth inhibition of other BALB/c lymphomas induced by Moloney virus (LSTRA), X-rays (RL male I) or urethane (UR-1) was evident in alloimmune mice. In vivo transfer of growth inhibition of YC8 was obtained with BALB/c anti-B10.D2 peritoneal exudate cells in a Winn assay. The ability of these alloimmune lymphoid cells to delay significantly the survival time of BALB/c mice injected with the mixture of immune cell and YC8 cells was abrogated by anti-Thy 1.2 plus C' treatment. In addition, nu/nu BALB/c mice were unable to develop resistance to YC8 outgrowth after alloimmunization. The results of this study show that: (1) syngeneic growth of a lymphoma can be prevented by alloimmunization with normal cells; (2) this cross-reaction involved non-H-2 antigens; (3) the phenomenon appeared to be mediated by T cells.

Analysis of the cellular immune response to and adoptive immunotherapy of a BALB/c lymphoma that cross-reacts with normal DBA/2 cells

“…Cytotoxic T lymphocytes (CTL) were able to lyse YC8 cells and DBA/2 or B10.D2 blasts while having little or no effect on several other syngeneic or allogeneic tumor or blast cells. These experiments confirm the presence on the surface of YC8 cells of DBA/2-1ike MiHA, a subset of which is shared with B10 background, a conclusion in keeping with previous transplantation studies in BALB/c anti-DBA/2 immune mice and by in vitro clonal analysis with anti-DBA/2 CTL [15,22]. In addition, we have recently found that such MiHA can also be defined by appropriate BALB/c anti-DBA/2 antisera (Ballinari et al submitted for publication).…”

Lysis of autologous human melanoma cells by in vitro allosensitized peripheral blood lymphocytes

“…It has also been reported that the frequency of these antitumor responses could be increased by in vitro stimulation of patient PBL (Pt-PBL) with autologous tumor cells or with allogeneic normal lymphocytes [15,17,19,23]. The possibility of increasing an autologous killing of cancer cells by alloimmunization, and the demonstration that a similar phenomenon may occur with different types of experimental tumors [10,12,14], prompted us to investigate whether in vitro ailosensitization of PBL could activate the killing of autologous malignant melanoma, a tumor which has received little attention in this respect in the previous studies.…”

DBA/2‐like minor histocompatibility antigens on a BALB/c lymphoma. A balb/c anti‐DBA/2 serum which lyses the tumor and blocks balb/c anti‐tumor and anti‐DBA/2 effectors

“…These findings further substantiate the presence of non-H-2 antigens of DBA/2 background on YC8 tumor cells. Altogether, the specificity of the blocking by OR-1, the pattern of CTL reactivity and its similarity with that obtained by histogenetic studies (Sensi et al, 1984;Parmiani et al, 1982) indicate that the antigens involved in these cross-reactions are MiHA of the DBA/ 2 background.…”

“…Previous work from our laboratory has shown a cross-reaction between the Moloney virus-induced BALB/c lymphoma YC8 and the non-H-2 alloantigens of DBA/2 tissues (Parmiani et al, 1982;Sensi et al, 1983Sensi et al, , 1984. It was of interest, therefore, to attempt to develop an antiserum directed against multiple MiHA of DBA/2 background to further analyze this phenomenon at the serological level and, if possible, to characterize the molecules involved.…”