Attached files
| file | filename |
|---|---|
| EX-99.1 - PRESS RELEASE - Cellular Biomedicine Group, Inc. | cbmg_991.htm |
| 8-K - CURRENT REPORT - Cellular Biomedicine Group, Inc. | cbmg_8k.htm |
EXHIBIT
99.2
2017 ASCO Annual Meeting Abstracts
The 2017 ASCO Annual Meeting abstracts were published on May 17,
2017 at 5:00 PM (EDT).
Target cell killing effects of CD20 targeting chimeric antigen
receptor T cells derived from the type II anti-CD20
antibody.
Sub-category: Cellular Immunotherapy
Category:
Developmental
Therapeutics—Immunotherapy
Meeting:
2017
ASCO Annual Meeting
Abstract
No: e14548
Citation:
J
Clin Oncol 35, 2017 (suppl; abstr e14548)
Author(s):
Yihong Yao, Xin Yao, Shigui Zhu, Wei Zhu, Zhiyuan Li, Qingxia Wang,
Lin Zhu, Anyun Ma, Yanfeng Li, Yutian Wei, Chengxiang Dai, Li
Zhang, Jiaqi Huang, Bizuo Liu; Cellular Biomedicine Group, Inc.,
Cupertino, CA
Abstract Disclosures
Abstract:
Background: Chimeric Antigen Receptor T cells (CAR-Ts)
targeting CD19 have shown very promising clinical outcomes in
treatment of B-cell linage hematological malignancies. However,
many patients with relapsed diseases were found to have
down-regulated/loss of CD19 surface expression after CD19 CAR-T
therapy. To solve this issue of CD19 single-targeting escape, we
explored the application of another B-cell antigen, CD20, for
targeted CAR-T therapy. Methods: We constructed four CD20 targeting CARs (all with
4-1BB co- stimulatory signaling) base on single-chain variable
fragments (scFV) derived from four well-studied CD20 specific
antibodies: Leu16,
Rituximab, Obinutuzumab, and Ofatumumab. Leu16,
Rituximab, and Obinutuzumab belong to the type I anti-CD20 antibody
family and appear to bind to different epitopes located on the
large loop of CD20, whereas Ofatumumab is the type II anti-CD20
antibody which has been shown to interact with the hydrophobic
residues on the small loop surrounding a deep binding cleft.
Results:
All four CAR-T cells can
specifically recognized CD20 positive target cells in our
pre-clinical studies. They all showed up-regulated
antigen-specific cell activation and high level of IFN-g
release upon CD20 stimulation, and CAR-T20-Ofatumumab cells
appeared to have significantly higher cell activation and
more than 2-fold increase in IFN-g release compared to the other
three CAR-T20 cells with their scFVs deriving from type I anti-CD20
antibodies. CAR-T20-Ofatumumab cells also showed higher
degranulation upon stimulation, and it displayed ~50% of increase
in ability to kill CD20 positive cells in cytotoxicity
assays. Conclusions:
Our data suggested that
CAR-T20-Ofatumumab has better in vitro function and appears to be a CAR superior to those
derived from other three antibodies. A possible explanation for
this observation is that Ofatumumab interacts with the hydrophobic
residues on the small loop, which is very close to cell membrane
and confers more extensive binding to the small loop with striking
slow off-rate. Our results suggest that CAR-Ts targeting CD20 with
the scFVs from the type II anti-CD20 antibody may have superior
cell killing effects.