Using the in vitro cytotoxic index against cells obtained from normal AKR/J mice, a method of predicting and paralleling the in vivo mouse toxicity of tolerant antileukemie, nontolerant

Data have been presented (2-4) indicating that anti AKR/J leukemia sera prepared in Dutch rabbits previously made tolerant to normal whole unfractionated AKR/J cells has little mouse toxicity, but marked toxicity for spontaneous AKR/J leukemia. Using precipitin reactions, attempts to correlate in vivo and in vitro activity of heterologous tolerant antisera against mouse tumors have failed [Ref. 7 and Levi and Scheehtman (un published data)]. However, Selka and Holeckova (5) and Holeckova et aL (1) have made sheep tolerant to the unfractionated leukoeytes of normal human beings, and subsequently immunized these tolerant sheep with leukocytes from leukemic patients. By the use of in vitro cytotoxic indexes, they differentiated these tolerant antileukemia vera from nontolerant antileukemia vera prepared in nontolerant sheep. The tolerant antileukemic serum attacked predominantly leukemie cells and the nontolerant antileukemia sera attacked about equally normal and leukemic WBC. These antisera were not reported to have been tested in vivo. In addi tion, the normal and leukemic cells came from different mdi viduals. This precludes the definitive conclusion that the tolerant antileukemia sera contain leukemia-specific antibodies un confused with normal histocompatibility antigens on the leu kemic cells. We considered it possible that the in vitro cytotoxic index of an antiserum might correlate with the in vivo activity observed for the same antiserum. This present paper deals with the in vitro assay of various anti sera by eytotoxic indexes. It was considered that these assays might predict and parallel the in vivo anti-normal tissue activity of the various antisera which had been prepared : (a) tolerant