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Patients are beginning to benefit from antibody based, cellular and vaccine approaches that are effective against genetically diverse and therapy-resistance cancers. BCG immunotherapy is now being used as a first line treatment for human bladder cancer and the introduction of prophylactic vaccination against Hepatitis B and HPV cancers is starting to show positive results. Following recent FDA approval for a vaccination against prostate cancer, and optimistic results in clinical trials for a vaccine targeting cancer antigens in lung cancer, cancer immunotherapy is now significantly impacting patient clinical management. Tumor Immunology and Immunotherapy provides an up-to-date and comprehensive account of cancer immunity and immunotherapy. It discusses our adaptive and innate immunity to cancer, the mechanisms underpinning our immune response, current approaches to cancer immunotherapy, and how tumour and host responses can circumvent effective anti-cancer immunity. The book examines recent results, publications and current areas of interest including 'immune editing' and the specific issues that are affecting the research and development of vaccines, providing insight into how these problems may be overcome, as viewed by world leaders in the field. Tumor Immunology and Immunotherapy will appeal to clinicians working in oncology and cancer immunotherapy, and research scientists including PhD and masters students, post-doctoral researchers and senior investigators.

Checkpoint blockade has demonstrated promising antitumor responses in approximately 10-40% of patients. However, the majority of patients do not make a productive immune response to their tumors and do not respond to checkpoint blockade. These patients may benefit from an effective vaccine that stimulates high-avidity T cell responses in combination with checkpoint blockade. We have previously shown that incorporating TRP-2 and gp100 epitopes into the CDR regions of a human IgG1 DNA (ImmunoBody®: IB) results in significant tumor regression both in animal models and patients. This vaccination strategy is superior to others as it targets antigen to antigen-presenting cells and stimulates high-avidity T cell responses. To broaden the application of this vaccination strategy, 16 NY-ESO-1 epitopes, covering over 80% of HLA phenotypes, were incorporated into the IB (SCIB2). They produced higher frequency and avidity T cell responses than peptide vaccination. These T cells were of sufficient avidity to kill NY-ESO-1-expressing tumor cells, and in vivo controlled the growth of established B16-NY-ESO-1 tumors, resulting in long-term survival (35%). When SCIB2 was given in combination with Treg depletion, CTLA-4 blockade or PD-1 blockade, long-term survival from established tumors was significantly enhanced to 56, 67 and 100%, respectively. Translating these responses into the clinic by using a combination of SCIB2 vaccination and checkpoint blockade can only further improve clinical responses.

Purpose: We have previously shown that supraoptimal signaling of high avidity T cells leads to high expression of PD-1 and inhibition of proliferation. This study was designed to see if this effect could be mitigated by combining a vaccine that stimulates high avidity T cells with PD-1 blockade. Experimental Design: We investigated the anti-tumor effect of a huIgG1 antibody DNA vaccine (SCIB1) and PD-1 blockade. Results: Vaccination of HLA-DR4 transgenic mice with SCIB1 induced high frequency and avidity T cell responses that resulted in survival (40%) of mice with established B16F1-DR4 tumors. SCIB1 vaccination was associated with increased infiltration of CD4 and CD8 T cells within the tumor but was also associated with upregulation of PD-L1 within the tumor environment. PD-1 blockade also resulted in increased CD8 T cell infiltration and an anti-tumor response with 50% of mice showing long term survival. In line with our hypothesis that PD-1/PD-L1 signaling results in inhibition of proliferation of high avidity T cells at the tumor site, the combination of PD-1 blockade with vaccination, enhanced the number and proliferation of the CD8 tumor infiltrate. This resulted in a potent anti-tumor response with 80% survival of the mice. Conclusions: There is a benefit in combining PD-1 blockade with vaccines that induce high avidity T cell responses and in particular with SCIB1.