Receptor Cell Engineering
Innovative technology with a growing list of
13 patients and several licensing partners.
What are CARs?
CARs are synthetic receptors that reprogram immune cells for therapeutic purposes. CARs contain three canonical domains for antigen recognition, T cell activation, and co-stimulation. The CAR cDNA is integrated in the T cell genome via lentivirus machinery. Autologous CAR-T cells are generated from the patient’s peripheral blood T cells and expand in the patient to eliminate the targeted tumor.
Our Unique Advantage
We can develop CAR-T cells with different scFv based on our proprietary antibodies and on antibodies that were first used for CAR-T cells (such as CD47)
- We developed proprietary methods of humanization of CAR scFv that can be used and a humanized CD19 that is available for drug development and licensing.
- BCMA-CAR-T cells were developed using several BCMA mAbs with different affinities that were validated both in vitro and in vivo. In addition, humanized BCMA CAR-T were developed and validated for efficacy.
- CD47 (do not eat me signal) CAR-T cells were developed to target solid tumor markers and validated in vitro and in vivo (CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth. Cancers, 2017, 017 Oct 21;9(10). pii: E139. doi: 10.3390/cancers9100139. PMID: 29065481).
- A list of >40 different cancer and cancer stem cell markers were developed based on our antibodies and validated in vitro and in vivo. In addition to CAR development, novel custom-generated antibodies can be developed by our scientists to target novel tumor markers.
Several Validated Approaches
I. CAR-T cells with decreased cytokines
II. Novel CAR co-activation domains
III. Hematological cancer: CD19/CD22, BCMA, CD123, CD4, CS1, CD24
IV. Solid cancer & cancer stem cell: CD47, ROR1, NGFR…
ProMab Biotechnologies (PMB) has developed many CAR-T and CAR-NK products based on nearly 20 years’ experience developing hybridoma cell lines, monoclonal antibodies (rabbit, mouse, and human), recombinant antibodies, and cancer stem cells. PMB’s CAR platform has patented innovations in the design of 3rd generation constructs, similar to the ones responsible for the astonishing clinical breakthroughs of CAR-T cells against various hematological malignancies.
PMB generates both mouse and fully human single-chain variable fragment (scFv) for the CAR constructs with over 3,000 hybridoma cell lines, 10^11 human phage display Fabs, and more than 5,000 mouse monoclonal antibodies in its library.
PMB has generated more than 30 types of CAR-T and CAR-NK cells targeting different tumor cells and cell lines expressing tumor-specific antigens. These genetically engineered cell lines are covered by 13 patents.
These CAR-T cells can be used with immunological modulators, tumor microenviroment invaders, or checkpoint inhibitors. In addition, PMB has developed sensitive real-time cytotoxicity assays (RTCA) for CAR-T cell validation in vitro and ex vivo. ProMab has also developed in vivo NSG/ NOG xenograft models to test CAR-T cell anti-cancer activity in hematological and solid cancers to validate the efficacy of the CAR-T and CAR-NK cells it has developed.
The technology that has been developed is available for licensing and has already been licensed to several biopharma companies, startups and hospitals worldwide.
- First CAR-T CRO in the world
- Human and Rabbit phage display platform
- GMP for lentivirus and CAR-T/NK production
- 2 locations in USA and China
- over 85 employees
Further Explanation of our CAR construct design
1 . We developed several bi-specific CAR-T cells such as CD19-CD22 and others to more specifically target tumor antigen in case of one tumor antigen such as CD19 or other loss.
2. ScFv has been linked to enzyme in order to regulate the tumor microenvironment (see work with Helix Biopharma).
3. We developed mutant CD28 domain that decrease cytokine secretion. Also novel domains such GITR can be used for CAR-T development. EGFR-CAR-T, Mesothelin-CART and Cd19-CAR-T with GITR domain can be used for research (GITR domain inside CAR co-stimulates activity of CAR-T cells against cancer, Frontiers in Bioscience, June 1, 2018; PMID: 29772559)
4. CAR-T with knock-down cytokines (IL-6) or check-point inhibitors such as PD-1 are available for development. In addition, combination with self-delivered (SD) RNA (RXi company) can be used with CAR-T cells.
5. We use different safety switches, i.e. truncated EGFR, RQR8 with CD34, Rituximab Antibody epitopes, and induciblecaspase-9 to regulate CAR-T cells.
6. CAR-tag such as CD19-Beams 1 can be used to image CAR-T cells in vivo (FLAG-tagged CD19-specific CAR-T cells eliminate CD19-bearing solid tumor cells in vitro and in vivo. Frontiers in Bioscience, 2017; PMID: 28410137)
Mesothelin-CD28DD Mutant CAR-T Cells Give Same or Higher Cytotoxic Activity Cells Against Ovarian A1847 Cancer while reduce > 4-5-fold IL-2 and IFN-g production.
Proprietary BeamTM Technology
A Selection of Our Collaborators
Dana-Farber Harvard Cancer Center
Massachusetts General Hospital
UF Shands Cancer Center
Roswell Park Cancer Institute
City of Hope