Comparison between immature and mature dendritic cells in a vaccination trial

Abstract

2562 Background: Dendritic cells may be responsible for awakening immunocompetence in cancer patients (pts). They can be administered therapeutically after loading with tumor antigens (immature dendritic cells, iDC), when it is hypothesized that they migrate to regional lymph nodes and mature in vivo, or they can be administered after in vitro maturation (mature dendritic cells, mDC). These two therapeutic modalities were compared in 19 pts with advanced melanoma or renal cell carcinoma (RCC) using iDC or mDC pulsed with autologous tumor lysate (ATL) and keyhole limpet hemocyanin (KHL), administered intradermally (id). Methods: DC were obtained from adherent mononuclear cells cultured with IL-4 and GM-CSF.ATL and KLH were added on the 6th day. On the 7th day iDC were used to vaccinate 9 pts, while mDC, obtained by a further 48-h culture with IL-1β, IL-6, TNFα and PGE2, were used in 10 pts. Results: Of the 9 pts (8 melanoma,1 RCC) treated with iDC, 4 showed stable disease (SD) of 19, 6, 6, 6 months' duration and 5 progressed (P). Four of the 9 pts had weak delayed-type hypersensitivity (DTH) skin reactions for KLH or ATL. Of the 10 pts (9 melanoma and 1 RCC) treated with mDC, there was 1 complete response (CR) (abdominal lymph nodes) of 10+ months' duration, with positive DTH for both ATL and KLH and onset of vitiligo,1 partial response (PR) (lung and lymph nodes) of 3 months' duration, with subsequent development of brain metastases, 1 mixed response (MR) (skin and lymph nodes) lasting 6 months with positive DTH for both ATL and KLH and subsequent development of brain metastases, 3 SD of 9 (RCC patient), 9 and 7+ months' duration with positive DTH for KLH (1 pt progressed with brain metastases), and 4 P (1 brain metastases), all with negative DTH for ATL. Conclusions: Intradermally administered mDC appear to have a more important therapeutic potential than iDC for anticancer vaccination. Results could be optimized by improving times and modalities of in vitro maturation, with a more specific selection of pts (more immunoresponsive and/or with minimal residual disease) and perhaps with chemoprevention of brain metastases. Partially financed by Ministry of Health Research Projects 2000, n. 352 and 2002, n.234. No significant financial relationships to disclose.