A phase Ib trial of an anti-idiotypic vaccine for Lewis Y (IGN 301) administered subcutaneously in patients with refractory solid tumors

Abstract

2586 Background: The Lewis Y (LeY) antigen is expressed on 60–90% of solid tumors with limited expression on normal tissue. This property has attracted interest to use LeY antigen as a vaccine in cancer immunotherapy. Use of an anti-idiotypic antibody (IGN 301) as an immunogenic surrogate for the LeY antigen is hypothesized to elicit a strong IgG response. We are conducting a phase I trial of IGN 301 to determine the safety, immunologic effects and antitumor activity with and without GM-CSF or IFN-α2b. Methods: Twenty-eight patients with solid tumor refractory to standard therapy enrolled in 2 cohorts. Cohort 1 received vaccine alone and cohort 2 received vaccine plus colony stimulating factor (GM-CSF). The immunogenicity of IGN 301 was assessed by measurement of the total humoral immune response. Seroconversion was assayed by ELISA and defined as a serum Ig titer of at least 1:100 against the murine type anti-idiotypic antibody used as vaccine antigen in IGN 301. T-cell reactivity was assessed by ELISPOT. Peripheral blood lymphocytes (PBLs) were isolated by Ficoll centrifugation and then tested for reaction against IGN 301, LeY and a series of positive and negative controls. Results: No patient experienced greater than grade 2 toxicity. Cohort 1 had a 64% seroconversion rate (9/14 patients) and cohort 2 had 60% (3/5 patients). T-cell reactivity was more frequent in cohort 1 (43%) versus cohort 2 (14%). The most frequent response observed was a Th1 phenotype (IFN-γ response). Only one patient from all evaluable was observed to have a Th2 (IL-4) response. Conclusions: IGN 301 was well tolerated without significant toxicities. Immunization induced a high rate of antibody seroconversion. Elicited T-cell immune response was predominantly Th1 phenotype. Further evaluation will assess the role and toxicity of IFN-α2b administration as an adjuvant with this vaccine. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Igeneon Igeneon