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Influence of Tumor-Host Differences at a Single Histocompatibility Locus (H-1) on the Antileukemic Effect of 1,3-Bis(2-chloroethyl)-1-nitrosourea (NSC 409962)¹

Microbiological Associates, Inc., Bethesda, Maryland 20014 (E. B., S. V.); Department of Pathology, School of Medicine, State University of New York at Buffalo, Buffalo, New York 14214 (G. C.); and National Cancer Institute, NIH, Bethesda, Maryland 20014 (A. G.)

Investigations were conducted with precisely defined genetic systems in order to determine whether a difference in a minor histocompatibility gene would be sufficient to result in immunological potentiation of the chemotherapeutic effect of a drug. Two congenic-resistant strains of mice differing from each other at the H-1 locus in linkage Group I, C57BL/10ScSn (B10) and C57BL/10.129 (5M), have been used to study the antileukemic activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against radiation-induced lymphomas of both strains transplanted into isogenic and congenic hosts. BCNU was more effective against B10 (H-1^c) lymphoma cells transplanted into 5M (H-1^b) mice than against cells transplanted into isogenic hosts. In contrast, the antitumor activity of BCNU against 5M lymphoma was essentially the same in 5M or B10 mice. Studies with grafts of normal marrow and lymphoma cells demonstrated that 5M mice are competent to react immunologically against H-1C antigen(s) of B10 donor cells. However, no response was observed in B10 mice grafted with 5M cells of H-1^b genotype. Thus, the H-1 allograft reactivity in this strain combination was unidirectional, as was the potentiation of the antileukemic effect of BCNU. The results indicated that host immune responses directed against antigen(s) of the tumor, specified by only a single minor histocompatibility gene, may be sufficient to produce a significant increase of the antileukemic effect of chemotherapy.

¹ Supported by Contracts PH-43-68-1283 and NIH 69-73 with Chemotherapy, National Cancer Institute, NIH, and by Grants T-476 of the American Cancer Society and AM-13,969 of the National Institute of Arthritis and Metabolic Diseases, NIH.

Received 3/25/70. Accepted 6/23/70.