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Rapid tumor regression in an Asian lung cancer patient following personalized neo-epitope peptide vaccination.

ABSTRACT: Personalized immunotherapy targeting tumor-specific mutations represents a highly promising approach to cancer treatment. Here, we describe an Asian lung squamous cell carcinoma patient demonstrating frank disease progression following chemotherapy and EGFR inhibitor treatment. Based on tumor mutational profiling and HLA typing, a saline-based multi-epitope peptide vaccine was designed and administered along with topical imiquimod as an adjuvant. Weekly neo-epitope peptide vaccination was followed by a rapid and dramatic regression of multiple lung tumor nodules, while a much larger liver metastasis remained refractory to treatment. Peripheral blood immune monitoring showed that specific cytotoxic T lymphocytes (CTLs) were induced primarily against peptide targets encompassing the widely shared EGFR L858R mutation, particularly one restricted to HLA-A*3101. Immunological targeting of this driver mutation may be of particular benefit to Asian lung cancer patients due to its relatively high prevalence within this patient population.

SUBMITTER: Li F

PROVIDER: S-EPMC5214696 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Rapid tumor regression in an Asian lung cancer patient following personalized neo-epitope peptide vaccination.

Li Fenge F Chen Caixia C Ju Tao T Gao Junqin J Yan Jun J Wang Peng P Xu Qiang Q Hwu Patrick P Du Xueming X Lizée Gregory G

Oncoimmunology 20161007 12

Personalized immunotherapy targeting tumor-specific mutations represents a highly promising approach to cancer treatment. Here, we describe an Asian lung squamous cell carcinoma patient demonstrating frank disease progression following chemotherapy and EGFR inhibitor treatment. Based on tumor mutational profiling and HLA typing, a saline-based multi-epitope peptide vaccine was designed and administered along with topical imiquimod as an adjuvant. Weekly neo-epitope peptide vaccination was follow ...[more]

PMID: 28123873

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Project description:IntroductionSince treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.MethodsSeventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.ResultsNo severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.ConclusionsPPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.Clinical trial registration numberUMIN000001844 (Registration Date: April 5, 2009).

Dataset Information

Rapid tumor regression in an Asian lung cancer patient following personalized neo-epitope peptide vaccination.

Publications

Rapid tumor regression in an Asian lung cancer patient following personalized neo-epitope peptide vaccination.

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