Stimulatory immunotherapy in mammary cancer

Abstract

Abstract Stimulation of rejection reactions by attenuated cancer cells is the most widely studied and the safest type of immunotherapy feasible at present. Transfer of serum and non-specific stimulation can increase the growth of cancers and carry risks of hypersensitivity reactions and granulomatous hepatitis. No such dangers accompany sensitization with irradiated cancer cells which augments the effect of subsequent irradiation of residual cancer in animals. Therefore we have examined the effects of autografts of irradiated cancer (AIC) added to conventional first treatment of mammary cancer by mastectomy and radiotherapy at a time when any residual or disseminated cancer could reasonably be expected to he small and more readily controlled by any systemic component of the putatively radiosensitizing immunotherapy. Two premenopausal and 14 postmenopausal women with prognostically unfavourable mammary cancer (11 with proved axillary lymph nodal metastases, I without such metastases and 4 in whom the nodal status was unknown because dissections were partial) were treated in this way 4–7 years ago. Twelve (75 per cent) patients are still alive. One survivor had many metastases in bones and subcutaneous tissues which appear to have regressed completely following chemotherapy. The other II survivors have no biochemical, clinical, radiological or scintigraphic signs of disseminated cancer. Three of the patients have died from metastases; one whose axillary nodal status was unknown developed cancer therein 52 months after first treatment, and another died of distant metastases after 50 months. The third had extensive axillary metastases at operation and died 6 months later. Another patient aged 78 years with unknown axillary nodal status died of pneumonia with no known metastases after 15 months. In vitro measurements of cancer-directed cellular immunity in the II survivors who are well have been compared with two age-matched groups of females. One group had comparable primary mammary cancer treated by mastectomy and postoperative radiotherapy but no AIC. A second age-matched group consisted of non-cancer-bearing females attending hospital for the treatment of simple conditions. These carefully controlled immunoassays of lymphocytotoxicity and leucocyte migration inhibition (performed twice) show that AIC strengthens cancer-directed cellular immunity, indicating a need for definition of the optimum application of AIC so that a controlled clinical trial may be designed to measure any benefit conferred by AIC upon patients bearing mammary cancers.