Challenges in the development of an autologous heat shock protein based anti-tumor vaccine

In spite of its long history, immunotherapy of cancer has led to only a few regulatory approved treatments, starting with interleukin (IL)-2 in renal cancer and melanoma and interferon in melanoma. Sipuleucel-T was approved for castrateresistant prostate cancer in 2010 and ipilimumab and pegylated interferon-α2b in 2011 for the treatment of metastatic and adjuvant melanoma respectively. Evidence of both humoral and cellular immune recognition of human cancer has been found and supports the hypothesis that specific autologous anti-tumor activity exists and may be enhanced with therapeutic activity. Published data from trials with autologous tumor vaccines documented activity although only one autologous-like vaccine has been approved in the US. The concept of enhancing specific innate anti-tumor activity is attractive and the approach developed by Srivastava et al., which is designed to present a unique peptide profile of each autologous tumor to the host immune system, using a heat shock protein fraction as both carrier and adjuvant, is conceptually appealing. In syngeneic rat tumors, this approach was shown to lead to anti-tumor activity and as described below evidence of activity was found in clinical trials. Vitespen (also known as Oncophage or HSPPC-96), is an immunotherapeutic agent derived from the tissue of a patient’s own tumor. Vitespen is a heat-shock protein (HSP) (glycoprotein 96)-peptide complex that is purified ex vivo from an individual patient’s tumor cells through Challenges in the development of an autologous heat shock protein based anti-tumor vaccine