2017
DOI: 10.1158/1078-0432.ccr-16-1423
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Characterization of an Immunogenic Mutation in a Patient with Metastatic Triple-Negative Breast Cancer

Abstract: The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer. A T… Show more

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Cited by 28 publications
(22 citation statements)
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“…91,92 Whole exome sequencing of the resected tumor identified candidate neoepitopes for further study, and TIL cultures were capable of identifying neoantigens processed by autologous antigen-presenting cells in vitro, in both class I and class II restricted fashion. 11,93 In a study of primary breast tumors, another group used an agonistic antibody against 4-1BB/CD137 during the initial TIL cultures and were able to generate more robust CD8 þ populations. In two of these patient-derived cultures, the expanded CD8 þ TILs were capable of mutation-specific recognition of class I predicted neoepitopes.…”
Section: Tumor Infiltration and The Ratio Of Cd8 þmentioning
confidence: 99%
“…91,92 Whole exome sequencing of the resected tumor identified candidate neoepitopes for further study, and TIL cultures were capable of identifying neoantigens processed by autologous antigen-presenting cells in vitro, in both class I and class II restricted fashion. 11,93 In a study of primary breast tumors, another group used an agonistic antibody against 4-1BB/CD137 during the initial TIL cultures and were able to generate more robust CD8 þ populations. In two of these patient-derived cultures, the expanded CD8 þ TILs were capable of mutation-specific recognition of class I predicted neoepitopes.…”
Section: Tumor Infiltration and The Ratio Of Cd8 þmentioning
confidence: 99%
“…Further, a relevant impact of the concomitant anti-PD1 therapy was unlikely since no expression of PD-L1 was detected in tumor biopsies. A similar approach was used for a pulmonary metastasis of a TNBC patient, where an immunogenic mutation was found among 72 nonsynonymous mutations (29). However, outcome data from this tailored TIL therapy was not reported.…”
Section: Tumor-infiltrating Lymphocytes (Til) Therapymentioning
confidence: 99%
“…Additionally, there are numerous therapy combinations that, if designed wisely, could have an impact on the efficacy of ACT, such as the combination with immune checkpoint blockade, post-transplant vaccination to improve T-cell persistence, and specific targeting of the TME immunosuppression. To date, few CD4 T-cell based therapies have been tested clinically [38,[53][54][55], but have shown clear evidence of clinical activity.…”
Section: Future Perspectivesmentioning
confidence: 99%