Active specific chemoimmunotherapy of lymph-node metastasis from a poorly immunogenic murine fibrosarcoma.
The fibrosarcoma MCA-SP, which was recently induced with methylcholanthrene (MCA) in C3H/HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA-SPN1, which bears a tumor-specific transplantation antigen (TSTA) cross-reactive with the parental line MCA-SP, was selected because of its proclivity for axillary lymph-node metastases. Although these lymph-node metastases were resistant to sinecomitant (post-excisional) immunity, they were susceptible to combined active and passive specific chemoimmunotherapy, using tumor-specific, 1-butanol-extracted, preparative isoelectric focusing-purified, TSTA (1 microgram weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re-stimulated in vitro with extracted TSTA and interleukin-2. This triple regimen both reduced the incidence of spontaneous lymph-node metastases, and prolonged the survival of tumor-bearing, as well as tumor-resected hosts. The results from local adoptive transfer assay using T-lymphocyte subpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2+ cytotoxic T-lymphocytes (CTL) mediated in vivo tumor-neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA-SP tumor and its lymph-node metastases.
Naito
K
K
Second Department of Surgery, Kyoto Prefectural University of Medicine.
Oka
T
T
Nomi
S
S
Yamagishi
H
H
Kahan
B D
BD
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D006649:Histocompatibility Antigens / Q000276:immunology*; D007114:Immunization; D007167:Immunotherapy; D008207:Lymphatic Metastasis; D008748:Methylcholanthrene; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen; D008748:Methylcholanthrene; D003520:Cyclophosphamide