Abstracts

TLR8 agonist VTX-2337 (motolimod) decreases monocytic myeloid-derived suppressor cells by inducing differentiation to mature antigen-presenting cells

There is increasing evidence that myeloid-derived suppressor cells (MDSCs) contribute to the progression of cancer by inhibiting tumor-directed immune responses and producing mediators that promote the growth and survival of tumor cells. While present at low numbers in the peripheral blood of healthy individuals, levels of circulating MDSC increase in cancer patients as tumors produce factors that drive both the expansion and recruitment of these immune cells.

Bexarotene increases tumor CD8+ T cells and improves response to conventional breast chemotherapy in the transgenic mouse mammary tumor model TgMMTV-neu

In breast cancer, increased immune infiltrate prior to neoadjuvant chemotherapy predicts improved pathologic complete response (pCR) and improved survival, however almost half of breast tumors have no CD8+ T cell infiltrate.

Vaccination targeting insulin-like growth factor binding protein-2 (IGFBP-2) in advanced ovarian cancer: Safety and immunogenicity

Background: Immunization against self-antigens can induce regulatory responses that inhibit the development of desirable Type I antitumor immune responses. Removing epitopes that bias toward a regulatory phenotype may enhance vaccine efficacy. We developed a novel IGFBP-2 targeting DNA plasmid vaccine capable of selectively inducing Type I immunity. IGFBP-2 is an important regulator of ovarian cancer invasiveness and metastases.

The ability of NSAIDs to inhibit polyp formation and stimulate Type I immunity is dose dependent

Background: Non-steroidal anti-inflammatory drugs (NSAID'S) have been studied as colorectal cancer (CRC) chemopreventive agents. Cyclooxygenase inhibitors have also been shown to have immune stimulatory effects on the tumor microenvironment; activating local antigen presenting cells and decreasing immune suppression. We compared the ability of two commonly used agents, celecoxib and naproxen to both inhibit adenoma formation as well as stimulate Type I immunity in mice when treatment was initiated at an early or later age

Multi-antigen vaccination for colon cancer treatment and prevention

Background: Despite the recent understanding that colon cancer is immunogenic and the level of tumor infiltrating T-cells identified is associated with disease outcome; few studies evaluate the immunomodulation of the disease. Cancer vaccines targeting colon cancer are limited and focus on only a few antigens such as CEA and MUC-1. Overexpression of self-proteins that are involved in cancer proliferation has been shown to be a mechanism by which self-proteins become immunogenic.

Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with recurrent or refractory ovarian cancer: A phase Ib trial reporting safety and clinical activity

Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. Here we report safety and clinical activity of avelumab in patients (pts) with previously treated, recurrent or refractory ovarian cancer (NCT01772004).

Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trial.

Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab (proposed INN) (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. Here we present results from a cohort of patients (pts) with recurrent or refractory ovarian cancer in an ongoing phase Ib study (NCT01772004 ). Methods: Pts with ECOG PS 0-1 received avelumab at 10 mg/kg Q2W.

Designing vaccines to prevent breast cancer recurrence or invasive disease

Introduction: With the emerging importance of the tumor immune environment in both invasive and preinvasive breast cancer, vaccine therapy may provide a well-tolerated, durable therapy for preinvasive breast cancer by preventing both recurrent preinvasive disease and progression to invasive disease. Preinvasive breast cancer is ideal for vaccines because the disease is slow growing and the patients are not immunosuppressed.

Bexarotene increases tumor CD8+ T cells and improves response to conventional breast chemotherapy in the transgenic mouse mammary tumor model TgMMTV-neu.

In breast cancer, increased immune infiltrate prior to neoadjuvant chemotherapy predicts improved pathologic complete
response (pCR) and improved survival, however almost half of breast tumors have no CD8+ T cell infiltrate. Evidence has
emerged that conventional breast cancer chemotherapy can increase CD8+ T cells (doxorubicin) and decrease the
immunosuppressive regulatory CD4+ T cells (paclitaxel and cyclophosphamide); therefore discovering well tolerated agents that

Identifying pre-diagnostic breast cancer antigens in transgenic mouse mammary tumor models for preventative vaccine development.

Preventative vaccine therapy may benefit women at high risk for breast cancer but currently it is impossible to identify women who
will develop breast cancer prior to tumor development to identify initiating cancer antigens. Immunocompetent transgenic mouse
mammary tumor models that are genetically similar to human breast cancer subtypes may identify pre-invasive antigens because
mice can be followed longitudinally. Comparing tumor growth characteristics in two mouse models (TgMMTV-neu is genetically

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