Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease. Tumors are poorly immunogenic and immunosuppressive, preventing T cell activation in the tumor microenvironment. Here, we present a microbial-based immunotherapeutic treatment for selective delivery of an immunogenic tetanus toxoid protein (TT 856-1313 ) into PDAC tumor cells by attenuated Listeria monocytogenes . This treatment reactivated preexisting TT-specific memory T cells to kill infected tumor cells in mice. Treatment of KrasG12D,p53R172H, Pdx1-Cre (KPC) mice with Listeria -TT resulted in TT accumulation inside tumor cells, attraction of TT-specific memory CD4 T cells to the tumor microenvironment, and production of perforin and granzyme B in tumors. Low doses of gemcitabine (GEM) increased immune effects of Listeria -TT, turning immunologically cold into hot tumors in mice. In vivo depletion of T cells from Listeria -TT + GEM–treated mice demonstrated a CD4 T cell–mediated reduction in tumor burden. CD4 T cells from TT-vaccinated mice were able to kill TT-expressing Panc-02 tumor cells in vitro. In addition, peritumoral lymph node–like structures were observed in close contact with pancreatic tumors in KPC mice treated with Listeria -TT or Listeria -TT + GEM. These structures displayed CD4 and CD8 T cells producing perforin and granzyme B. Whereas CD4 T cells efficiently infiltrated the KPC tumors, CD8 T cells did not. Listeria -TT + GEM treatment of KPC mice with advanced PDAC reduced tumor burden by 80% and metastases by 87% after treatment and increased survival by 40% compared to nontreated mice. These results suggest that Listeria -delivered recall antigens could be an alternative to neoantigen-mediated cancer immunotherapy.

No abstract

No abstract

1526 Background: The use of pre-implantation genetic diagnosis (PGD) to select against BRCA mutated embryos for in-vitro fertilization (IVF), introduces complex choices for patients with pathogenic BRCA mutations. We sought to describe the uptake of and attitudes toward this technology in this patient population. Methods: We conducted a prospective survey study at a single institution in New York City affiliated with both a Cancer Center and Fertility Center, to assess attitudes and utilization of PGD. Cancer Center staff distributed surveys to patients with known BRCA mutations between April and August 2018. Survey participation was voluntary and anonymous. Survey data were analyzed using descriptive statistics and two-tailed t tests. Results: 80 survey responses were collected. A majority of the patient population identified as Caucasian (87.5%, 70) and Jewish (52.5%, 42). The survey was distributed to all age groups; however 81% (65) were between 26 and 45 years of age. 63.8% (51) had heard of PGD prior to completing the survey, while 36.3% (29) had not. Only 40% of respondents (32) felt sufficiently educated regarding PGD. 35% (28) patients met with an REI, of whom 6.3% (5) utilized IVF with PGD, and 21.3% (17) plan to use IVF with PGD in the future. 11.3% (9) wish they had known about this technology prior to starting a family, 20% (16) would not have used PGD had they known about it prior to childbearing. Reasons respondents were unlikely to pursue PGD included: cost (38.8%, 31), completed childbearing (25%, 20), medical risk (18.8%, 15), and ethical concerns (16.2%, 13). Patients gave cost estimates for PGD ranging from $500 - $120,000. There was no statistically significant correlation between likelihood of pursuing PGD and parity (p = 0.45), religion (p = 0.78), education level (p = 0.13), number of family members affected by BRCA mutations (p = 0.20) or by cancer (p = 0.11). Conclusions: Overall, a small number of patients with pathogenic BRCA mutations utilize PGD. A minority of survey respondents felt adequately educated about PGD. Reported barriers to uptake were varied, and there was a wide range of cost estimates reported. Our results suggest that increased patient education regarding PGD in BRCA mutation carriers is warranted.