A novel role for autologous tumour cell vaccination in the immunotherapy of the poorly immunogenic B16-BL6 melanoma.
The growth of immunogenic tumours stimulates the generation of tumour-sensitized, but not functional, pre-effector T cells in the draining lymph nodes. These pre-effector cells can mature into effector cells upon in-vitro stimulation with anti-CD3 and IL-2. In the current study, using a defined, poorly immunogenic tumour, B16-BL6 melanoma, the pre-effector cell response was not evident during progressive tumour growth but was elicited by vaccination with irradiated tumour cells admixed with Corynebacterium parvum. After anti-CD3/IL-2 activation, these cells were capable of mediating the regression of established pulmonary metastases. The efficacy of the vaccine depended on the doses of both tumour cells and the adjuvant. While higher numbers of tumour cells were more effective, an optimal dose (12.5 micrograms) of C. parvum was required. The dose of irradiation was not a critical factor. After vaccination, kinetic studies revealed that the pre-effector cell response was evident 4 days later and declined after 14 days. These observations illustrate the potential role of active immunization in the cellular therapy of cancer.
Geiger
J D
JD
Department of Surgery, University of Michigan, Ann Arbor 48109.
Wagner
P D
PD
Shu
S
S
Chang
A E
AE
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D003013:Clostridium / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000528:radiation effects; D016219:Immunotherapy, Adoptive / Q000379:methods; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology / Q000528:radiation effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D000906:Antibodies; D017252:CD3 Complex; D007376:Interleukin-2; D011994:Recombinant Proteins