Immunoisolation of tumor cells: generation of antitumor immunity through indirect presentation of antigen.
In recent years, a number of cancer therapies have been developed based on the augmentation of the immune response in the tumor-bearing individual. We have developed a novel approach to such therapies, using a membrane-bound immunoisolation device containing tumor cells to enhance the immune response of mice to the adenocarcinoma, MCA-38. Use of an immunoisolation device for cancer immunotherapy has several advantages. First, safety is enhanced because the reintroduced tumor cells are sequestered within the device. Second, the immunoisolation device permits introduction and maintenance of live cells that can stimulate the immune system for extended periods. Finally, the cells can be quantitatively removed at the end of the treatment period. Cells derived from the murine adenocarcinoma cell line MCA-38 were implanted into mice within a membrane-enclosed (immunoisolation) device. After 3 weeks, the animals were challenged by injection of free tumor cells. All of the control animals (lacking implants or with empty devices) developed tumor at the challenge site, whereas all of the animals that received devices containing tumor cells remained tumor free. The animals also remained tumor free after a second challenge. It is our hypothesis that antigens shed from tumor cells within the device are taken up by antigen-presenting cells of the host and thus indirectly initiate the activation of the immune system.
Geller
R L
RL
Gene Therapy Unit, Baxter Healthcare Corporation, Round Lake, Illinois 60073, U.S.A.
Neuenfeldt
S
S
Levon
S A
SA
Maryanov
D A
DA
Thomas
T J
TJ
Brauker
J H
JH
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D002470:Cell Survival; D005260:Female; D007158:Immunologic Techniques / Q000295:instrumentation*; D007167:Immunotherapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured