Clinical trial NCT03407040: Generation of Cancer Antigen-Specific T-cells From Human Induced Pluripotent Stem Cells (iPSC) for Research and Potential FutureTherapy
Official title: Generation of Cancer Antigen-Specific T-cells From Human Induced Pluripotent Stem Cells (iPSC) for Research and Potential Future Therapy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Gastrointestinal Cancers
Breast Cancer
Pancreatic Cancer
Melanoma
Lung Cancer
Keywords: Blood
Tissue
Immunotherapy
Tumor
Somatic
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2018-01-23
Enrollment: 98
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a cancer diagnosis enrolled on protocol 03-C-0277

Brief summary: Background:

Researchers want to test if certain cells can be re-programmed into stem cells. Stem cells can keep reproducing for a long time. Cells made by stem cells can be turned into different types of cells. These include cancer-fighting cells, skin cells, etc. The stem cells generated in this study will be used to make specific tumor-fighting cells that can recognize different types of mutations in cancer cells. They may also help identify new tumor mutations that may not have been identified yet.

Objectives:

To test if a certain type of tumor-fighting cells can be re-programmed into stem cells.

Eligibility:

Participants in another Surgery Branch protocol who are at least 16 years old

Design:

Participants already gave samples of blood and/or tumor tissue in the other protocol. They do not need to come back to the clinic or give any other samples.

Participants will give consent for their samples to be used in this study.

Researchers will obtain cells from the samples. They will grow those cells in the lab. They will create stem cells from them.

Researchers will do genetic tests on the samples.

Most tests will not show important health results. But if they do, the participant will be invited to talk to a genetic counselor and get more detailed testing to confirm the results.

Some of the samples and results will be stored indefinitely. They may be used in future research. No personal information will be stored with them.

...

Detailed description: Background:

T-cells are potentially curative for patients with metastatic cancer, but many patients with cancer have T-cells that are terminally differentiated , a condition associated with treatment failure. We have observed that less differentiated T-cells have a greater capacity to proliferate, persist, and destroy large cancer deposits. Advances in regenerative medicine might allow the generation of rejuvenated T-cells from induced pluripotent stem cells (iPSC).

Objectives:

To reprogram patient specimens into induced pluripotent stem cells (iPSC) and differentiate them into different types of somatic cells with the goal to produce cancer antigen-specific T-cells.

To make stored specimens and/or data available to approved research laboratories and investigators.

Eligibility:

Patients enrolled on the National Cancer Institute Surgery Branch (NCI-SB) Cell Harvest protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols).

Patients willing to be consented on this protocol.

Design:

Cells and tissue obtained previously under protocol 03-C-2077.

Reprogramming of cells and tissue into iPSC lines.

Derivation of iPSC lines into T-cells and iPSC progeny capable of supporting T-cell differentiation.

Generation of an iPSC-derived thymic organoid.

Screening of tumor antigen specificity for regenerated T-cells.

In vivo analysis of regenerated T-cells.

Eligibility criteria: * INCLUSION CRITERIA:
* Patients with a cancer diagnosis enrolled on protocol 03-C-0277.
* Willing and able to provide informed consent
* Patients must be greater than or equal to 15 years of age.

EXCLUSION CRITERIA:

-Healthy donors enrolled on protocol 03-C-0277.

Primary outcomes:
measure: Production of cancer antigen-specific T-cells
timeFrame: Approximately 10 years
measure: Availability of stored specimens and/or data
timeFrame: Approximately 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Steven A Rosenberg, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nishimura T, Kaneko S, Kawana-Tachikawa A, Tajima Y, Goto H, Zhu D, Nakayama-Hosoya K, Iriguchi S, Uemura Y, Shimizu T, Takayama N, Yamada D, Nishimura K, Ohtaka M, Watanabe N, Takahashi S, Iwamoto A, Koseki H, Nakanishi M, Eto K, Nakauchi H. Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell. 2013 Jan 3;12(1):114-26. doi: 10.1016/j.stem.2012.11.002.
citation: Vizcardo R, Masuda K, Yamada D, Ikawa T, Shimizu K, Fujii S, Koseki H, Kawamoto H. Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells. Cell Stem Cell. 2013 Jan 3;12(1):31-6. doi: 10.1016/j.stem.2012.12.006.
citation: Parent AV, Russ HA, Khan IS, LaFlam TN, Metzger TC, Anderson MS, Hebrok M. Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development. Cell Stem Cell. 2013 Aug 1;13(2):219-29. doi: 10.1016/j.stem.2013.04.004. Epub 2013 May 16.