Immunotherapy offers an attractive approach to the control of cancer. Passive immunotherapy with specifically sensitized cells holds particular promise, but requires the ability to consistently develop large numbers of lymphoid cells capable of eliminating the tumor in vivo and an understanding of T cell functions and interactions. Newly developed methods for isolation, characterization, expansion, long-term growth and cloning of lymphoid cells in culture, make it possible to achieve these goals. Reliable experimental models are now required to test and refine this potentially very valuable mode of treatment and determine its applicability to naturally occurring, established cancers. In an unique model system developed in our laboratory, acute leukemia in mice undergoes predictable, immunologically-mediated, spontaneous regression. Normal T cell and macrophage functions are essential for regression to occur. In a consistent fraction of clinically regressed animals, the leukemia spontaneously recurs. Under support of this grant, we have shown that leukemia regression can be efficiently induced in progressor leukemia mice by transfer of in vitro cultured T cells that are specifically reactive to virus/leukemia cell antigens. This immunotherapy is effective even in fully leukemic animals and requires no concurrent or prior adjunctive treatment such as irradiation or cytotoxic drugs. Helper Lyt 1+ cells are implicated in causing permanent disease cures, while cytotoxic Lyt 2+ cells cause temporary leukemia remissions.
The aims of the present study include: complete characterization of the effector cells, their antigenic specificity and mechanism of action in vivo; determination of the involvement of lymphokines in successful immunotherapy; and development and characterization of effective immunotherapeutic protocols for prevention and treatment of leukemic recurrence, the outstanding problem in cancer management.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA033939-06
Application #
3171690
Study Section
Experimental Immunology Study Section (EI)
Project Start
1983-02-01
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Amc Cancer Research Center
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80214
Pourbohloul, S C; Thurlow, S M; Furmanski, P et al. (1992) Induction of permanent regression of Friend virus (FV) leukemia by adoptive transfer of T helper and not T cytotoxic cells. Leuk Res 16:881-7
Furmanski, P; Johnson, C S (1990) Macrophage control of normal and leukemic erythropoiesis: identification of the macrophage-derived erythroid suppressing activity as interleukin-1 and the mediator of its in vivo action as tumor necrosis factor. Blood 75:2328-34
Johnson, C S; Chang, M J; Thurlow, S M et al. (1990) Immunotherapeutic approaches to leukemia: the use of the Friend virus-induced erythroleukemia model system. Cancer Res 50:5682S-5686S
Braunschweiger, P G; Johnson, C S; Kumar, N et al. (1990) The effect of adrenalectomy and dexamethasone on interleukin-1 alpha induced responses in RIF-1 tumours. Br J Cancer 61:9-13
Johnson, C S; Thurlow, S M; Furmanski, P (1989) Lymphokine-activated killer cell plus recombinant interleukin-2 therapy of erythroleukemia in mice. Leukemia 3:91-6
Johnson, C S; Keckler, D J; Topper, M I et al. (1989) In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythro Blood 73:678-83
Johnson, C S; Chang, M J; Furmanski, P (1988) In vivo hematopoietic effects of tumor necrosis factor-alpha in normal and erythroleukemic mice: characterization and therapeutic applications. Blood 72:1875-83
Braunschweiger, P G; Johnson, C S; Kumar, N et al. (1988) Antitumor effects of recombinant human interleukin 1 alpha in RIF-1 and Panc02 solid tumors. Cancer Res 48:6011-6
Johnson, C S; Thurlow, S M; Furmanski, P (1986) Induction of leukemia regression in mice by immunotherapeutic transfer of T-lymphocytes. Cancer Res 46:183-9
Johnson, C S; Marcelletti, J F; Furmanski, P (1986) Infection of haematopoietic stem cells in mice with Friend virus induced erythroleukaemia. Cell Tissue Kinet 19:455-65