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|Ref Type||Journal Article|
|Authors||Kalli KR, Block MS, Kasi PM, Erskine CL, Hobday TJ, Dietz A, Padley D, Gustafson MP, Shreeder B, Puglisi-Knutson D, Visscher DW, Mangskau TK, Wilson G, Knutson KL|
|Title||Folate Receptor Alpha Peptide Vaccine Generates Immunity in Breast and Ovarian Cancer Patients.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2018 07 01|
|Abstract Text||Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients.Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later.Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months.Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype. Clin Cancer Res; 24(13); 3014-25. ©2018 AACR.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|FR alpha peptide vaccine||Multi-epitope Folate Receptor Alpha Peptide Vaccine||FR alpha peptide vaccine is a peptide vaccine comprised of multi-epitopes of the folate receptor alpha, which may induce cytotoxic immune response against FR alpha-expressing tumors (PMID: 29545464).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||ovarian cancer||not applicable||FR alpha peptide vaccine||Phase I||Actionable||In a Phase I trial, FR alpha peptide vaccine demonstrated safety, induced durable immune response against Folr1 in ovarian cancer patients who completed standard treatment, and all patients (n=14) remained alive 2 years after initial immunization, with a median relapse-free survival of 528 days; however, T cell response did not correlate with tumor Folr1 expression level (PMID: 29545464; NCT01606241).||29545464|
|Unknown unknown||Her2-receptor negative breast cancer||not applicable||FR alpha peptide vaccine||Phase I||Actionable||In a Phase I trial, FR alpha peptide vaccine demonstrated safety, induced durable immune response against Folr1 in hormone receptor-positive, ERBB2 (HER2)-negative breast cancer patients who completed standard treatment, and all patients (n=8) remained alive 2 years after initial immunization, with a median relapse-free survival not reached; however, T cell response did not correlate with tumor Folr1 expression level (PMID: 29545464; NCT01606241).||29545464|