Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma

Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET. Metastati...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Cancer research communications Ročník 3; číslo 5; s. 821 - 829
Hlavní autoři: Shah, Payal D., Huang, Alexander C., Xu, Xiaowei, Orlowski, Robert, Amaravadi, Ravi K., Schuchter, Lynn M., Zhang, Paul, Tchou, Julia, Matlawski, Tina, Cervini, Amanda, Shea, Joanne, Gilmore, Joan, Lledo, Lester, Dengel, Karen, Marshall, Amy, Wherry, E. John, Linette, Gerald P., Brennan, Andrea, Gonzalez, Vanessa, Kulikovskaya, Irina, Lacey, Simon F., Plesa, Gabriela, June, Carl H., Vonderheide, Robert H., Mitchell, Tara C.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Association for Cancer Research 01.05.2023
Témata:
Breast Cancer
Clinical Trial Results
Humans
Immunotherapy
Immunotherapy, Adoptive - adverse effects
Melanoma - therapy
Middle Aged
RNA - metabolism
Skin Cancers
T-Lymphocytes
Triple Negative Breast Neoplasms - therapy
ISSN:2767-9764, 2767-9764
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET. Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated. Mean age was 50 years (35-64); median Eastern Cooperative Oncology Group 0 (0-1); median prior lines of chemotherapy/immunotherapy were 4/0 for TNBC and 1/3 for melanoma subjects. Six patients experienced grade 1 or 2 toxicity. Toxicities in at least 1 patient included anemia, fatigue, and malaise. One subject had grade 1 cytokine release syndrome. No grade 3 or higher toxicity, neurotoxicity, or treatment discontinuation occurred. Best response was stable disease in 4 and disease progression in 3 subjects. mRNA signals corresponding to CAR T cells were detected by RT-PCR in all patients' blood including in 3 subjects on day +1 (no infusion administered on this day). Five subjects underwent postinfusion biopsy with no CAR T-cell signals seen in tumor. Three subjects had paired tumor tissue; IHC showed increases in CD8 and CD3 and decreases in pS6 and Ki67. Intravenous administration of RNA-electroporated cMET-directed CAR T cells is safe and feasible. Data evaluating CAR T therapy in patients with solid tumors are limited. This pilot clinical trial demonstrates that intravenous cMET-directed CAR T-cell therapy is safe and feasible in patients with metastatic melanoma and metastatic breast cancer, supporting the continued evaluation of cellular therapy for patients with these malignancies.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2767-9764
2767-9764
DOI:10.1158/2767-9764.CRC-22-0486