Intratumoral Therapy II: In Vitro and In Vivo Immunologic Testing and Therapy Options

In a prospective randomized trial in patients with metastatic melanoma we compared two agents that had been used for metastatic melanoma intratumoral injections. Each patient had progressive metastatic disease no longer surgically controllable. Multiple metastases included satellitosis in the form of progressive nodules around the previously excised original melanoma site, and/or in-transit metastases in the form of observable tumor nodules progressing in a linear fashion toward a lymph node bearing area. As patients were receiving intratumoral injections, serially collected blood samples were tested for general immunologic reactivity and anti-melanoma reactivity. Specificity controls included breast cancer and lung cancer extracts. Additionally, as a measure of cell-mediated immunity, the patients were serially skin tested against antigens to measure general and melanoma-specific immunity. Depending on the patients’ clinical courses, we have divided the patients retrospectively into groups whose clinical courses were either better or worse than their cohorts, and determined the relationship between the immune testing and the clinical courses that the patients were experiencing as the serial testing was being conducted. Additionally, in a group of similar patients that were ‘cured for life’, we analyze their treatment in light of therapeutic attempts made by others to similarly haptenize melanoma antigens. We describe potential synergies between newly discovered melanoma therapies and intratumoral injection treatments and point out potential combination therapies that may offer the potential for enhancement of antitumor effects without increased systemic toxicity, a desirable goal now that combinations of recently acceptable immunotherapies have been associated with severe potential toxicities including death.