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Immune responses to syngenetic tumours

University of British Columbia

The anti-tumour activity of normal C57BL/6J (B6) spleen cells that were sensitized to the syngeneic tumour, EL4 and expanded in inter-leukin 2 (IL2) were assessed in vitro and in vivo. Cultured cells demonstrated strong cytotoxic responses in vitro. However, although the cytotoxic T lymphocytes (CTL) preferentially killed EL4 these cells were nonspecific in the sense that they also killed syngeneic B6 LPS blast as well as the allogeneic DBA/2 (D2) tumour, P815, albeit to a lesser degree. Nonspecific activity appeared as a consequence of expanding the cultures in IL2-containing medium. The effector cells were shown to be Thy-1⁺. In studies which followed the clearance of ¹²⁵I-iododeoxy- uridine- (¹²⁵IUdR) labelled tumour cells from B6 mice, it was found that mice treated with B6 anti-EL4- cultured cells survived longer than untreated mice. However, studies with labelled cultured cells indicated that the cultured cells have a short half life in vivo (≤ 10% remaining after 48 hr). Thus, the long term effects of cultured cells in vivo is most likely due to the activation of the host's immune system. In agreement with in vitro results, B6 anti-EL4 cultured donor cells were not absolutely specific for EL4 in the sense that (C57BL/6J x DBA/2J)F1 (BDF1) mice treated with these cells also showed an enhanced clearance of ¹²⁵IUdR P815. However, the mean survival time (MST) to P815 relative to controls was not enhanced. The in vivo activity of D2 anti-P815 effector cells were also determined. Unlike B6 anti-EL4 system, these cells specifically enhanced the elimination of P815 tumour cells; however, they failed to prolong the MST of the mice to P815 when compared to controls. Two out of five B6 mice treated with B6 anti-EL4 cultured cells survived a lethal challenge of EL4. The frequency of CTL precursors from the two immune and normal spleen cells were 1/800, 1/950 and 1/4000, respectively. Furthermore, CTL from primed spleen cells were more specific for EL4 than normal spleen cells. When used in conjunction with cyclophosphamide (CY), B6 anti-EL4 cultured cells were more effective in conferring protection against EL4 in B6 mice. CY by itself also led to a higher rate of EL4 clearance from B6 mice. The use of cultured cells in immunotherapy against syngeneic tumour is discussed.

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2010-04-20

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http://hdl.handle.net/2429/23960

Microbiology and Immunology

University of British Columbia

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