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In our opinion the most urgent needs to improve patient outcomes are: 1) a deeper ability to measure cancer immunobiology, and 2) increased availability of agents that, coupled with predictive biomarkers, will be used to tailor anti-cancer immunity. Tailoring effective immunotherapy will entail combinations of immunotherapeutics that augment priming of anti-cancer immunity, boost expansion of effector and memory cells of the T, B and NK lineage, amplify innate immunity and relieve checkpoint inhibition. Alternatives to inducing adaptive immunity to cancer include synthetic immunology that incorporate bi-specifics that target T cells to cancer or adoptive immunotherapy with gene-modified immune cells.

Meeting abstracts Analysis of tumor-infiltrating immune cells using quantitative immunohistochemistry (IHC) has proved to be a powerful prognostic biomarker in colon cancer [[1][1], [2][2]]. Similar observations have been made in patients with oral, head and neck squamous cell carcinoma (OHNSCC)

Meeting abstracts Generation of a therapeutic immune response against a diverse set of antigens expressed by a patient's cancer is a central goal of cancer immunotherapy. This goal is important because diverse responses may prevent escape of antigen loss variants. To accomplish this goal we have

Because the benefits of immune checkpoint blockade may be restricted to tumors with pre-existing immune recognition, novel therapies that facilitate de novo immune activation are needed. DRibbles is a novel multi-valent vaccine that is created by disrupting degradation of intracellular proteins by the ubiquitin proteasome system. The DRibbles vaccine is comprised of autophagosome vesicles that are enriched with defective ribosomal products and short-lived proteins, known tumor-associated antigens, mediators of innate immunity, and surface markers that encourage phagocytosis and cross-presentation by antigen presenting cells. Here we summarize the rationale and preclinical development of DRibbles, translational evidence in support of DRibbles as a therapeutic strategy in humans, as well as recent developments and expected future directions of the DRibbles vaccine in the clinic.

Recent work by Rosenberg, et. al. demonstrates the role of mutated epitopes in natural anti-cancer adaptive immunity. This has led some to hypothesize that cancer vaccines may need to induce or augment immunity against mutated and potentially patient-specific epitopes to achieve therapeutic efficacy. In the case of whole-cell cancer vaccines, this could happen either indirectly through epitope spreading, or directly against 'hotspot' mutation sites on oncogenes. The purpose of this study is to determine whether patients who received an irradiated GM-CSF-secreting whole-cell prostate cancer vaccine, GVAX, preferentially developed humoral immune responses against mutated proteins. Archived pre-treatment and week 11 serum from patients enrolled on an investigator-initiated combination immunotherapy trial were assessed using protein arrays (ProtoArray, Invitrogen). Antibody responses that were increased in the week 11 sera were considered increased as a result of immunotherapy. Next we utilized reported liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics and whole-exome sequencing data for LNCaP and PC3, the two cell lines contained in prostate GVAX, to assess whether the targets of elevated antibody responses detected by protein array were directed preferentially against the mutated proteins contained in the vaccine. Of the 7554 different human proteins included in our analysis, a mean of 63 candidate responses were identified for each patient (SD = 43). These candidate responses were then compared to published non-synonymous mutations in LNCaP and PC3, published LC-MS/MS proteomics on the protein content of LNCaP and PC3, and randomized lists of proteins on the array [1-3]. Preliminary analysis suggests that there was no increase in antibody responses above background against proteins with published cell-line specific mutations. However, the number of antibody responses was increased against proteins identified by mass spectrometry (p = 0.017). This result suggests that when GM-CSF secreting whole-cell vaccine is not combined with other immunotherapies, vaccine alone may be insufficient to induce or augment immune responses against mutated epitopes. Supported by The Prostate Cancer Foundation, DAMD PC02009, Robert W. Franz, the Chiles Foundation, ARCS Foundation: Portland, and the OCTRI, OSLER TL1 award.