Active specific immunotherapy of minimal residual tumor: Excision plus neuraminidase‐treated tumor cells

Tumor growth can be severely inhibited and total regression occasionally induced when mice bearing firmly established transplantable syngeneic tumors are challenged with living tumor cells which have been treated in vitro with Vibrio cholerae neuraminidase (VCN) plus mitomycin C. Tumors greater than 1 cm in diameter will not regress. The present experiments were designed to determine if immunotherapy could be effective if the tumor mass were surgically reduced. Three tumors previously shown to be susceptible to active specific immunotherapy with VCN‐treated tumor cells were utilized. Two time periods were selected, that in which VCN‐treated tumor cells will normally inhibit growth (12–15 days post inoculation) and that time period after which VCN‐treated tumor cells alone are insufficient to inhibit growth (25 days post inoculation). Three types of tumor excision were investigated; minimal reduction in tumor mass by wedge excision, subtotal reduction of tumor mass by tumor enucleation, and attempts at total excision with narrow margins. The combination of subtotal or total excision plus challenge with VCN‐treated tumor cells was significantly more effective than either excision or immunotherapy alone. The best results were obtained with the MC‐43 methylcholanthrene‐induced fibrosarcoma and a transplantable mammary adenocarcinoma (M‐2). No synergistic or additive effect of specific active immunotherapy and surgical therapy was noted in the B16 melanoma, which tends to metastasize early after implantation and grows as an indistinct infiltrative local tumor mass rather than a well‐pronounced local growth. Results strongly suggest that the reduction in tumor mass by surgical means might allow active specific immunotherapy to become an effective anti‐tumor adjunct.