Advanced ovarian cancer: Vaccination site draining lymph node as target of immuno-modulative adjuvants in autologous cancer vaccine

摘要

Tumor as source of tumor associated antigens (TAA) and sentinel lymph node (SLN) configure the first interaction between the malignant disease and the patient’s immune system. As consequence of this interaction, a local immune response is elicited inside the SLN. Tumor’s cytokines reach the SLN conditioning its cellular microenvironment to produce local permissive immune responses. This local tolerogenic immunity is decisional because it starts a systemic also permissive immunity. The tumor progresses.To counteract this mechanism, we have designed a medical procedure to create an immunotherapeutic site (ITS) that reproduces, distantly from the tumor, a TAA source and a draining lymph node but with a cellular microenvironment conditioned to promote local protective instead of permissive immune responses. Due to ITS decisional role, this local protective immunity starts a systemic anti-tumoral immune response.In progressive ovarian cancer, we tested an ITS using the autologous thermostable hemoderivative-cancer vaccine as TAA source and granulocyte macrophage-colony stimulant factor plus etoposide, injected both at the vaccination site, as conditioner of the draining lymph node cellularity. The immunophenotyping of lymph node cell populations showed that ITS acquired a locally protective immune profile T-regulatory-cells/activated-antigen presenting-cells and systemically increased the antiprogressive effect of the tested vaccine.