MSS05: IMMUNOLOGIC EFFICACY OF E39 & E39â VACCINATION IN A PHASE I/IIA TRIAL IN OVARIAN & ENDOMETRIAL CANCER PATIENTS
Jessica L Cindass, MD1, Annelies T Hickerson, MD1, Tommy A Brown II1, Kaitlin M Peace1, John W Myers III1, Timothy J Vreeland2, Diane F Hale1, Doreen O Jackson1, Julia M Greene3, John S Berry IV4, Guy T Clifton1, Garth S Herbert1, George E Peoples5; 1Brooke Army Medical Center, San Antonio, TX, 2University of Texas MD Anderson Cancer Center, Houston, TX, 3Tripler Army Medical Center, Honolulu, HI, 4Womack Army Medical Center, Fort Bragg, NC, 5Cancer Vaccine Development Program, San Antonio, TX
Background: The treatment options for cancer are ever-evolving and now include vaccines targeting tumor-specific immunogenic peptides to induce tumor cytolysis. Folate binding protein (FBP) is a tumor-associated antigen (TAA) highly expressed in most endometrial and ovarian cancers, shielded from the normal immune system. The most promising FBP peptides are E39 and an attenuated form, E39’ (aka J65). In our most recent phase I/IIa trial we evaluated an E39+GM-CSF inoculation series at 3 doses (VG) vs controls (CG) as well as booster vaccination with E39 and or E39’ after the initial inoculation series. Here we present the immunologic data from this phase I/IIa trial.
Methods: Patients with ovarian or endometrial cancer who were disease-free after standard of care therapy but at risk for recurrence were enrolled. HLA-A2+ patients were enrolled in the VG, with the first 9 patients vaccinated in a 3+3 dose escalation of 100mcg, 500mcg, and 1000mcg, and the remaining patients receiving 1000mcg inoculations. Vaccine was given every 3-4 weeks for a total of 6 doses. Patients were then offered booster vaccination and randomized to receive E39 or E39’. FBP expression level was measured on the resected disease. Immunologic response was measured by delayed type hypersensitivity (DTH) and ELISPOT in the VG.
Results: A total of 29 patients were vaccinated, 9 patients received boosters with E39 and 9 with E39’. Mean DTH prior to the initial dose of E39 was 5.74mm and after final dose was 10.33mm (p = 0.018). Mean overall ELISPOT change over time through 18 months was +69.1 when compared to baseline (p=0.675). At 18 months post vaccination, mean ELISPOT increased by +97.1 in 1000mcg vs -57.0 in in <1000mcg patients (p = 0.047). At 18 months post vaccination, mean ELISPOT in patients with above average initial DTH increased by +255.33 from baseline, while those with below initial DTH showed a decrease from baseline of -0.75 (p = 0.004). Immunological analyses were not significantly different between FBP high/low expression or E39 vs E39’ booster (p < 0.05).
Conclusions: E39 demonstrated significant overall immunogenicity on in vivo testing as measured by DTH. Ex vivo analysis (ELISPOT) suggests that E39 is more immunogenically efficacious in patients with baseline immunity to FBP (indicated by with > average initial DTH) and those who are optimally dosed (1000mcg). FBP expression level and E39 vs E39’ use in booster inoculations did not significantly impact in vivo or ex vivo immunogenicity.