Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial

被引：16

作者：

Hegde, Meenakshi ^{[1
,2
,3
,4
]}

Navai, Shoba ^{[1
,2
,3
,4
]}

DeRenzo, Christopher ^{[1
,2
,3
,16
]}

Joseph, Sujith K. ^{[1
,2
,3
,4
]}

Sanber, Khaled ^{[1
,2
,5
]}

Wu, Mengfen ^{[4
]}

Gad, Ahmed Z. ^{[1
,2
,3
,6
]}

Janeway, Katherine A. ^{[7
]}

Campbell, Matthew ^{[1
,2
,3
]}

Mullikin, Dolores ^{[1
,2
,3
]}

Nawas, Zeid ^{[1
,2
,3
]}

Robertson, Catherine ^{[2
]}

Mathew, Pretty R. ^{[1
,2
,3
]}

Zhang, Huimin ^{[2
]}

Mehta, Birju ^{[2
]}

Bhat, Raksha R. ^{[1
,2
,3
]}

Major, Angela ^{[8
]}

Shree, Ankita ^{[1
,2
,3
]}

Gerken, Claudia ^{[1
,2
,3
]}

Kalra, Mamta ^{[1
,2
,3
]}

Chakraborty, Rikhia ^{[1
,3
,4
]}

Thakkar, Sachin G. ^{[2
]}

Dakhova, Olga ^{[2
]}

Salsman, Vita S. ^{[1
,2
,3
]}

Grilley, Bambi ^{[1
,2
,3
,4
]}

Lapteva, Natalia ^{[2
,8
]}

Gee, Adrian ^{[1
,2
,3
]}

Dotti, Gianpietro ^{[9
]}

Bao, Riyue ^{[10
,11
]}

Salem, Ahmed Hamed ^{[12
]}

Wang, Tao ^{[4
]}

Brenner, Malcolm K. ^{[1
,2
,3
,4
,5
]}

Heslop, Helen E. ^{[1
,2
,3
,4
,5
]}

Wels, Winfried S. ^{[13
,14
,15
]}

Hicks, M. John ^{[1
,8
]}

Gottschalk, Stephen ^{[1
,2
,3
,4
,16
]}

Ahmed, Nabil ^{[1
,2
,3
,4
,8
]}

机构：

[1] Texas Childrens Hosp, Baylor Coll Med, Texas Childrens Canc & Hematol Ctr, Houston, TX 77030 USA

[2] Houston Methodist Hosp, Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[4] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA

[5] Baylor Coll Med, Dept Med, Houston, TX USA

[6] Baylor Coll Med, Interdept Program Translat Biol & Mol Med, Houston, TX USA

[7] Boston Childrens Hosp, Dana Farber Canc Inst, Harvard Med Sch, Dept Pediat, Boston, MA USA

[8] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA

[9] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA

[10] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA

[11] UPMC Hillman Canc Ctr, Pittsburgh, PA USA

[12] Ain Shams Univ, Dept Clin Pharm, Fac Pharm, Cairo, Egypt

[13] Inst Tumor Biol & Expt Therapy, Georg Speyer Haus, Frankfurt, Germany

[14] German Canc Consortium DKTK, Partner Site Frankfurt Mainz, Frankfurt, Germany

[15] Goethe Univ, Frankfurt Canc Inst, Frankfurt, Germany

[16] St Jude Childrens Res Hosp, Dept Bone Marrow Transplantat & Cellular Therapy, Memphis, TN USA

来源：

NATURE CANCER | 2024年 / 5卷 / 06期

关键词：

YOUNG-ADULT PATIENTS; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; ONCOLOGY-GROUP; B-CELL; OSTEOSARCOMA; CHEMOTHERAPY; TRASTUZUMAB; EFFICACY; IMMUNOTHERAPY;

D O I：

10.1038/s43018-024-00749-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) +/- cyclophosphamide (Cy): 1 x 108 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 x 108 CAR+ T cells per m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044. In this phase 1 trial, Hegde et al. treat 13 individuals with advanced sarcoma with lymphodepletion followed by HER2-specific CAR T cells, which were found to be safe and showed antitumor activity.

引用

页码：880 / 894

页数：31

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