Combined immunotherapy and radiation induce cellular and humoral immune responses to tumor-associated antigens and prolong survival of patients with advanced cancers.

Abstract

Immunotherapy is effective in treating patients with a variety of cancers We developed and employed an immunotherapeutic protocol that combined intra-tumor injection of autologous immature dendritic cells , with standard of care radiation to treat patients with a variety of different advanced solid tumors. Pre and post treatment peripheral blood mononuclear cells ( PBMC) were assayed for their capacity to kill autologous tumor cell lines that had been established from patients with different advanced solid tumors. PBMC obtained post treatment were cytotoxic to autologous but not allogeneic tumor cell lines. Cytotoxic activity increased as relative numbers of CD8+-CD56+ dual positive lymphoid cells increased in PBMC obtained post treatment. The autologous tumor cell line directed cytotoxicity was shown to be mediated by both innate and adaptive immune mechanisms. Cytotoxicity of PBMC obtained post treatment was enhanced after co-culture with autologous and not allogeneic tumor cell line lysates. Antibody activity to mesothelin, a tumor associated antigen expressed in a variety of solid tumors, increased in post treatment serum samples from lung cancer patients. These sera mediated antibody directed cellular cytotoxicity ( ADCC) to mesothelin expressing tumor cell lines. SSurvival of 96 patients with a variety advanced cancers patients treated on this protocol over a 3 year period and followed for 1000+ days was significantly increased in patients with low tumor burden ( lesion at <5 sites with diameters < 3cm) (Km= <0.0001) regardless of malignancy. These findings support application of this combination of immunotherapy and radiation in the treatment of cancer patients with advanced disease