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Innovative TME-specific Pro-CAR T-cells for Immunotherapy of Solid Tumors

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA224652-01
Agency Tracking Number: R41CA224652
Amount: $224,991.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-05-01
Award End Date (Contract End Date): 2020-04-30
Small Business Information
1168 LEGEND OAKS DR
Chapel Hill, NC 27517-6165
United States
DUNS: 081124946
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 JINGJING LI
 (919) 843-3634
 jingjing.li@panacisebio.com
Business Contact
 RIHE LIU
Phone: (919) 391-8968
Email: rihe.liu@trapimmune.com
Research Institution
 UNIVERSITY OF NORTH CAROLINA AT CHAPEL H
 
ROOM 102 CARRINGTON HALL
CHAPEL HILL, NC 27599
United States

 Domestic nonprofit research organization
Abstract

Abstract
This project seeks to develop the next generation pro CARs that are inactive in normal tissues but selectively
activated in the tumor microenvironmentTMEThe project is based on our previous development of a novel
class of chimeric antigen receptors on the basis of single domain antibody mimics that recognize ErbB family
membersSDAErbBon the surface of cancer cellsWe propose two specific aims in this projectThe first aim is
to develop a pro SDAErbB CAR that is inactive in normal tissues due to the blockade of the antigen binding sites
by an N terminal prodomainbut selectively activated in TME through proteolytic cleavage of the prodomain by
matrix metalloproteinase MMPhighly expressed in TME or by fibroblast activation proteinFAPabundant in the reactive tumor stromal fibroblastsThe second aim is to develop a novel class of CAR that
integrates a chemotactic chemokinewhich upon being delivered by CAR T cells and locally released to TMEwill attract endogenous cytotoxic T cellsCTLsto the tumor site to provide higher and enduring antitumor
efficacy in a TME specific mannerThe two complementary CAR T cell platforms have significant advantages
on high efficacy and specificity to tumor cells but very low side toxicity and improved safety to normal cellsand
therefore the great potential to be applied to treat numerous solid tumorsAlthough we focus on EGFRand
HERspecific CARs in this projectthe same technology platform can be applied to develop numerous other
CARs that target neoantigensfor the treatment of solid tumors of interest Project Narrative
This project is directed at developing the next generation pro CAR T cells that are inactive in normal tissues
but selectively activated in the tumor microenvironment for the treatment of ErbB expressing solid tumors

* Information listed above is at the time of submission. *

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