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. Immunotherapie active et Specifique sur la Tumeur Residuelle Minimale: Excision et Traitement des Cellules Tumorales a la Neuraminidase La croissance tumorale peut ětre fortement inhibee et une regression totale peut se produire occasionnellement lorsque des souris porteuses de tumeurs syngeniques transplantables bien etablies subissent l'attaque de cellules tumorales vivantes qui ont ete traitees in vitro par la neuraminidase de Vibrio cholerae (VCN) et la mitomycine C. Les tumeurs de plus d'un centimetre de diametre ne regresseront pas. Ces experiences visaient a determiner si l'immunotherapie peut ětre efficace lorsque la masse tumorale est resequee. Les auteurs ont utilise trois tumeurs qui s'etaient deja averees sensibles a l'immunotherapie active et specifique avec des cellules tumorales traitees au VCN. Deux periodes ont ete choisies, celle ou les cellules tumorales traitees au VCN inhibent normalement la croissance (12–15 jours apres l'inoculation) et celle apres laquelle ces cellules ne suffisent plus a inhiber la croissance (25 jours apres l'inoculation). Les auteurs ont etudie trois types d'excision: reduction minimale de la masse tumorale par excision partielle, reduction subtotale par enucleation, et tentative d'excision totale avec une marge tres faible. Une excision subtotale ou totale combinee a l'attaque des cellules tumorales traitees au VCN etait beaucoup plus efficace que l'excision ou l'immunotherapie. Les meilleurs resultats ont ete obtenus avec le fibrosarcome MC-43 induit par le methylcholanthrene et avec un adenocarcinome mammaire transplantable (M-2). Aucun effet synergistique ou additionnel de l'immunotherapie active et specifique et du traitement chirurgical n'a ete observe avec le melanome B16, qui a tendance a produire des metastases peu apres l'implantation et qui se presente sous la forme d'une masse tumorale locale infiltrante et indistincte plutǒt que sous celle d'une tumeur locale bien determinee. Les resultats semblent bien signifier que la reduction chirurgicale de la masse tumorale peut faire de l'immunotherapie active et specifique un complement efficace du traitement antitumoral.