Northampton Electronic Collection of Theses and Research

Phase I trial of ImmunoBody in melanoma patients

Patel, P. M., Durrant, L. G., Ottensmeier, C., Mulatero, C., Lorigan, P., Plummer, R., Cunnell, M., Metheringham, R. L., Brentville, V. A., Machado, L., Daniels, I. and Hannaman, D. (2014) Phase I trial of ImmunoBody in melanoma patients. Poster presented to: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, McCormick Place, Chicago, Illinois, 30 May - 03 June 2014. (Unpublished)

Item Type: Conference or Workshop Item (Poster)
Abstract: ImmunoBody is a DNA vaccine encoding a human IgG1 antibody with T cell epitopes grafted into its CDR regions. SCIB1 has 3 epitopes grafted from gp100 and one from TRP-2 antigens. The vaccine targets dendritic cells in vivo and stimulates high avidity T cells which result in elimination of established tumors in pre-clinical models. A clinical trial was conducted to determine safety and its ability to induce cellular immune responses. Methods: The vaccine was administered via Intramuscular injection with electroporation at 3 weekly intervals for 3 vaccinations, then at 3 and 6 months. In part 1 of the study,one patient with Stage III and 8 with stage IV melanoma were given escalating doses of SCIB1. The 4mg dose was selected for an expansion cohort (part 2) in fully resected patients, 8 with stage III and 6 with stage IV melanoma. Due to lack of toxicity a five further patients with stage IV M1b disease were given 8mg doses. Results: No dose-limiting toxicities were observed. The most common adverse event was injection site pain. 4/6 patients in the 2mg/4mg cohorts who received >3 doses of SCIB1, are still alive with a median survival time of 26 months. One patient had multiple tumor lesions which all decreased in size or disappeared following treatment except for one lesion which was resected. Immunohistochemistry demonstrated strong expression of PD.L1 on the tumor cells. All patients in part 2 remain alive and only three have progressed. The median survival time in Part 2 is 17 months from study entry and 22 months from diagnosis of metastatic disease. In part 1, one patient in the 0.4mg cohort, all three patients in the 2mg dose cohort and two patients in the 4mg dose cohort mounted an immune response to the vaccine-encoded antigens. 4/5 patients in the 8mg cohort made a γIFN elispot response after T cell expansion in-vitro with frequencies exceeding 2% of blood lymphocytes. In part 2, all 14 patients responded immunologically. Six patients responded to all 4 epitopes, five patients responded to 3 epitopes and 3 patients responded to 2 epitopes. Conclusions: We demonstrate that SCIB1 is safe. Of 25 evaluable patients, 23 have shown immune responses following repeat dosing with 2 -8 mg of SCIB1. Detection of an objective clinical response and overall survival times are encouraging. Clinical trial information: NCT01138410.
Additional Information: Abstract also published in: Journal of Clinical Oncology, 2014 ASCO Annual Meeting Abstracts. Vol 32, No 15_suppl (May 20 Supplement), 2014: 3061
Subjects: Q Science > QR Microbiology > QR180 Immunology > QR189.5.D53 DNA vaccines
R Medicine > RM Therapeutics. Pharmacology > RM270 Immunotherapy. Serotherapy
R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology
Creators: Patel, Poulam M, Durrant, Lindy G, Ottensmeier, Christian, Mulatero, Clive, Lorigan, Paul, Plummer, Ruth, Cunnell, Michelle, Metheringham, Rachael L, Brentville, Victoria A, Machado, Lee, Daniels, Ian and Hannaman, Drew
Northamptonshire and East Midlands: Health
Faculties, Divisions and Institutes: University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society > Sports, Exercise & Life Sciences
University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Ageing Research Centre
Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences
Research Centres > Centre for Health Sciences and Services
Research Centres > Centre for Physical Activity and Life Sciences
Date: June 2014
Date Type: Presentation
Event Title: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting
Event Dates: 30 May - 03 June 2014
Event Location: McCormick Place, Chicago, Illinois
Event Type: Conference
Language: English
Status: Unpublished
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