T-Cell Therapy Against Patient-Specific Cancer Mutations
Human cancers contain genetic mutations that are unique to each patient. Some of the mutated peptides are immunogenic, can be recognized by T cells, and therefore, may serve as therapeutic targets.
Scientists at the National Cancer Institute's Surgery Branch developed a method to identify T cells that specifically recognize immunogenic mutations expressed only by cancer cells. The scientists identified cancer-specific mutations from a patient with widely metastatic cholangiocarcinoma by sequencing tumor samples and comparing with normal cells. Using tandem minigene constructs encoding all of the mutations expressed by a patient's tumor, the inventors identified T cells that recognized the immunogenic mutations from the same patient. These mutation-reactive T cells have the potential to eliminate the cancer cells while sparing normal tissues since normal tissues do not express the mutations. The mutation-reactive T cells were expanded in vitro, and then infused as a highly pure population back into the same patient. The patient experienced tumor regression when treated with this approach.
Competitive Advantages:
- This patient-specific therapy has the potential application to most epithelial cancers, which account for about 90% of cancer deaths in the United States.
- Personalized mutation-specific T cells recognize mutations harboring tumor cells only and spare normal tissues. This therapy has no tissue toxicities comparing to traditional chemotherapy and radiotherapy.
- The infusion of a highly pure population of these mutation-specific T cells may maximize therapy and result in regression of all target lesions.
Commercial Applications:
- Personalized immunotherapy with mutation-reactive T cells for mediating tumor regression in patients with immunogenic mutations.
- Mutation-reactive T cell therapy especially beneficial for cancer patients refractory to other therapies.
- A research tool to identify patient-specific immunogenic mutations in the tumor.
Patents
- Patent Cooperation Treaty
(PCT) PCT/US2014/058796
Filed on 2014-10-02
Status: Expired - Australia
National Stage 2014407539
Filed on 2014-10-02
Status: Issued - Canada
National Stage 2963362
Filed on 2017-03-31
Status: Pending - China
National Stage 201480082932.3
Filed on 2014-10-02
Status: Abandoned - European Patent
National Stage 14796317.7
Filed on 2014-10-02
Status: Issued - Japan
National Stage 2017-517662
Filed on 2014-10-02
Status: Issued - US
National Stage 15/514,942
Filed on 2017-03-28
Status: Abandoned - Japan
Divisional (DIV) 2020-066108
Filed on 2020-04-01
Status: Abandoned - Australia
Divisional (DIV) 2021200388
Filed on 2021-01-21
Status: Issued - European Patent
Divisional (DIV) 22166152.3
Filed on 2022-03-31
Status: Pending - Japan
Divisional (DIV) 2022-077983
Filed on 2022-05-11
Status: Issued - Belgium
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - Denmark
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - France
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - Germany
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - Italy
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - The Netherlands
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - Norway
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - Spain
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - Sweden
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - Switzerland
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - United Kingdom
European patent (EP) 14796317.7
Filed on 2014-10-02
Status: Issued - US
Divisional (DIV) 18/147,786
Filed on 2022-12-29
Status: Pending