Immunology Research Center and the Departments
of Medical Genetics. Surgery. Pediatrics and Human Oncology. University
of Wisconsin. Madison. Wisconsin 53706. USA
* This work is supported in part by NIH grants CA-16836. AI-11576.
AI-08439. CA-20409 and CA-14520. and National Foundation March of
Dimes £rants CRBS 246 and 6- 76-213. This is paper no.164 from the
Immunobiology Research Center and paper no.2270 from the Laboratory
of Genetics. The University of Wisconsin. Madison. Wisconsin 53706.
A major goal in our understanding of leukemia involves the study
of cell surface antigens on the leukemic cells that are not present
on patients' normal cells of the same type. These antigens. if they
serve as tumor rejection type antigens. are commonly referred to
as tumor associated transplantation antigens. One approach to the
study of these antigens, which is also of potential interest with
regard to cellular immunotherapy of leukemia, involves attempts
to generate cytotoxic cells against autologous leukemia cells. The
approaches that we have used have largely been based on earlier
and concurrent studies involving recognition and response to alloantigens
in the mixed leukocyte culture (MLC) and cell mediated Iympholysis
(CML) assays. Two general approaches have been used, both of which
are presented in this paper. In each case the background studies
of the allogeneic system are given as a reference.
We have presented the rationale for the in vitro approaches that
we have taken for generating cytotoxic lymphocytes capable of lysing
autologous leukemia cells or leukemia cells from HLA identical siblings.
Two different approaches have been used, both of which are based
on earlier findings concerning the antigenic and cellular interactions
involved in the generation of strong cytotoxic responses to alloantigens
in mixed leukocyte culture.