Posts Tagged ‘TCRLs’

Next-generation Universal Cell Immunotherapy startup Adicet Bio, Menlo Park, CA is launched with $51M Funding by OrbiMed

Reporter: Aviva Lev-Ari, PhD, RN

On 1/27/2016 Adicet Bio announced the acquisition of Applied Immune Technologies (AIT)

Applied Immune Technologies (AIT) was acquired by Adicet, 1/27/2016.

AIT is a drug development company specializing in T-Cell Receptor-Like (TCRL) antibodies that are targeted to intracellular-derived peptides for a variety of therapeutic and diagnostic applications. AIT is also focused on identification and validation of novel therapeutic targets.

Therapeutic Antibodies
AIT’s core technology platforms encompass the identification and validation of novel MHC-based targets, as well as development of therapeutic Human Recombinant T-Cell Receptor-Like (TCRL) antibodies with the unique ability to bind with these intracellular peptide/MHC complexes with the specificity of cytotoxic T-cell killer cells.
AIT’s technologies enable the generation of a rich pipeline of therapeutic TCRL antibodies for intracellularly-derived, disease-specific targets which normally are not accessible to conventional antibodies. TCRL antibodies also have diagnostic applications in vaccine design, validation and monitoring, as well as analysis of antigen presentation in disease.

Immune System Explained 

Our immune system is composed of two arms: antibodies and T cells.

Soluble antibody molecules can bind to cell surface expressed proteins with high affinity and specificity. Upon binding, they can recruit effector cells of the immune system such as macrophages and Natural Killer (NK) cells, or mediate a biological signal into cells. Antibodies constitute today the most important class of targeted therapeutics in the bio-pharmaceutical industry.HOWEVER, analysis of the human proteome reveals that only 20% of human proteins are expressed on the cell surface. The remaining 80% of the human proteome is intracellular, and is therefore not accessible by conventional antibodies for therapeutic targeting clinical applications. Thus, there is an urgent need for the development of novel therapeutic antibodies against these intracellular based targets.

T cells mediate cellular immunity. CD8+ Cytotoxic T cells (CTLs) are the most potent effector cells of the immune system because they can recognize and kill diseased cells in a highly specific manner. They recognize intracellular proteins due to their ability to bind to the cell surface-expressed MHC-peptide complex, which presents peptides derived from intracellular proteins. Upon specific recognition of the MHC-peptide complex by the T-cell receptor (TCR), the CTLs undergo activation, proliferation and expansion, leading to destruction of the target diseased cells. HOWEVER, T cells are very difficult to manipulate for therapeutic applications and thus their advantage in recognizing intracellular targets is very difficult to apply for clinical therapeutic purposes.



AIT – Technology

TCRL™ Antibodies

AIT’s innovative solution is a platform technology for the development of human recombinant T-Cell Receptor-Like (TCRL) antibodies capable of targeting intracellular-derived peptides. These 3rd generation antibodies combine the advantages of both arms of the immune system. They are capable of binding to targets with high affinity and specificity like conventional antibodies. In addition, they can recognize and bind to intracellular-derived peptides presented on the MHC complex with the same degree of specificity as T cells, but without being limited by the regulatory mechanisms imposed on T cells.

TCRL antibodies enable us to identify and validate intracellular-expressed disease-specific targets and make them available for cell surface targeting. AIT’s platform technology further enables the generation of highly specific therapeutic antibodies against these intracellular-derived targets, which can bind to them on the cell surface and kill the diseased cells only, without effecting healthy cells. Thus, disease-specific targets that are expressed inside diseased cells are transformed into targets that can be recognized by soluble antibodies on the cell surface.

This breakthrough harnesses the power of the cellular arm of the immune system to attack diseased cells with soluble, readily made human monoclonal antibodies. Distinct from conventional monoclonal approaches that only attack cell surface-associated proteins, AIT’s TCRL technology addresses the far more abundant intracellular proteome. The combination of these features opens up entirely new vistas for the development of highly specific 3rdgeneration antibodies for the treatment of cancer, viral, and autoimmune diseases.



EpiTarget™ Discovery

EpiTarget is a unique approach for the discovery and validation of novel therapeutic MHC-based targets that can be applied to the isolation and characterization of new TCRL antibodies against a variety of disease-related intracellular targets.

The EpiTarget approach combines bioinformatic analysis and mass spectroscopy strategies to identify target peptides presented on MHC molecules that are differentially expressed on diseased cells of various histological origins.

The large intracellular proteome, which is not accessible for antibody-based recognition, can serve as a huge pool for new target discovery and a strong pipeline for therapeutic and diagnostic TCRL antibodies by integration of proteomic strategies with the TCRL technology.




Makler, O., Oved, K., Netzer, N., Wolf, D., Reiter, Y. Direct visualization of the dynamics of antigen presentation in human cells infected with cytomegalovirus revealed by antibodies mimicking TCR specificity. Eur. J. Immunol. 40: 1552-1562, 2010.

Klechevsky, E., Flamar, A.L., Cao, Y., Liu, M., Thompson-Snipes, L., O’Bar, A., Zurawski, S., Reiter, Y., Zurawski, G., Banchereau, J. Cross-priming CD8+ T cells by  targeting antigens to human dendritic cells through DCIR. Blood 116:1685-97, 2010.

Dahan, R., Tabul, M., Chou, Y.K., Meza-Romero, R., Andrew, S., Ferro, A.J., Burrows, G.G., Offner, H., Vandenbark, A.A., Reiter, Y. TCR-like antibodies distinguish conformational and functional differences in auto-reactive idiotopes present on two vs. four-domain MHC class II/peptide complexes. Eur. J. Immunol. 41:1465-79,2011.

Dahan, R, Reiter, Y. T-cell-receptor-like antibodies – generation, function and applications. Expert Rev Mol Med. 14:e6, 2012.

Noy, R., Epel, M., Haus-Cohen, M., Klechevsky, E., Makler, O., Michaeli, Y., Denkberg, G., Reiter, Y. T-cell receptor-like antibodies: novel reagents for clinical cancer immunology and immunotherapy. Exp. Rev. Anticancer Ther. 5(3) 2005.

Michaeli, Y., Sinik, K., Cohen, M., Reiter, Y:. Protein Instability and Aberrant Intracellular Processing of Tyrosinase Lead to High Presentation of HLA-A2/Tyrosinase Complexes on the Surface of Melanoma Cells. Eur. J. Immunol. In press 2012.



Next-generation immunotherapy startup Adicet is launched with $51M Funding by OrbiMed

Reporter: Aviva Lev-Ari, PhD, RN


biotech investing JP Morgan 2016Aya Jakobovits, former founder and CEO of Kite Pharma and current venture partner at OrbiMed, is heading up a new, next-gen immunotherapy startup – backed by an impressive $51 million Series A.

The Bay Area upstart, called Adicet Bio, is keeping very quiet about its underlying platform. Jakobovits emphasized in a phone interview, however, that the platform is meant to develop “universal immune cell therapy” – meaning it should be broadly applicable for a number of diseases, including cancer, autoimmune disease and inflammation.

It’s launching with news of an acquisition, however: Adicet just bought Israeli immunotherapy company Applied Immune Technologies, which focuses on the intracellular proteome.

“There’s a very good correlation between AIT and Adicet,” Jakobovits said.

AIT develops T-Cell Receptor-like antibodies that are targeted, through the Major Histocompatibility Complex (MHC), toward disease-linked peptides in cells. Adicet’s plan is to generate monoclonal antibodies that have affinity and high specificity to this MHC complex, she said.

Jakobovits said there’s no correlation or link between Kite Pharma and Adicet – in technology or in business dealings.

The financing round was led by OrbiMed with participation from Novartis Venture Fund and Pontifax.



Adicet Bio Announces Closing of $51 Million Series A Financing and Acquisition of

Applied Immune Technologies

Menlo Park, CA (January 27, 2016): Adicet Bio, Inc. (“Adicet”), a biopharmaceutical company focused on the development of next-generation cell immunotherapies, announced today that it closed a $51 million Series A financing. Adicet also announced the acquisition of Applied Immune Technologies, Ltd. (“AIT”), an Israel-based company that develops immunotherapies directed to the intracellular proteome.

The financing was led by OrbiMed and also included Novartis Venture Fund and Pontifax.

“These significant financial resources will allow Adicet to progress its universal immune cell therapy (“uICT”) platform technology and related products and advance AIT’s programs and product pipeline,” said Aya Jakobovits, Ph.D., Founder, President and Chief Executive Officer of Adicet. “AIT’s technologies, capabilities, and intellectual property highly complement those of Adicet and position the combined company to become a leader in next-generation immunotherapy products for cancer and other indications.

Adicet was founded by Aya Jakobovits and OrbiMed. Previously, Dr. Jakobovits served as the President and founding CEO of Kite Pharma, Inc. Before joining Kite Pharma, she served as Executive Vice President, Head of Research and Development at Agensys, Inc., which became an affiliate of Astellas Pharma Inc. in a deal valued at up to $537 million. Before its acquisition, she served as Agensys’ Senior Vice President, Technology and Corporate Development and Chief Scientific Officer. Prior to Agensys, Dr. Jakobovits served as the Director, Discovery Research and Principal Scientist at Abgenix, Inc., which was spun out of Cell Genesys, Inc. and based on the XenoMouse® technology developed under her leadership. Abgenix was acquired by Amgen Inc. for $2.2 billion.

AIT specializes in generating and developing T-Cell Receptor-Like (“TCRL”) antibodies with high affinity and specificity to disease-specific intracellular peptides presented on the cell surface by the major histocompatibility complex (“MHC”). AIT also established Epitarget, a proprietary technology to identify and validate novel disease-specific peptide targets. AIT technology is based on work by Prof. Yoram Reiter, a world leader in the research of immunotherapies directed to the intracellular proteome. AIT will continue its operations in Israel as Adicet’s wholly-owned subsidiary.

Following the financing and acquisition, the Adicet Board of Directors will include Jonathan Silverstein and Carl Gordon, General Partners and Co-Heads of Global Private Equity at OrbiMed, Aya Jakobovits, Florent Gros, Managing Director at Novartis Venture Fund, and Erez Chimovits, Managing Director at OrbiMed Israel.

“We are excited to join forces again with Aya, a prominent figure in the field of immunotherapy with a track record of growing successful biotechnology companies,” said Carl Gordon.

“We look forward to building a leading immunotherapy company,” said Jonathan Silverstein. “The AIT acquisition expands Adicet’s platform technologies and its product pipeline.”

About Applied Immune Technologies, Ltd.

Applied Immune Technologies Ltd. (“AIT”) pioneered and advanced the generation and development of TCRLs for therapeutic and diagnostic applications in cancer, inflammation, autoimmune, and infectious diseases. AIT’s TCRLs are directed to disease-specific peptide-MHC complexes and are aimed at delivering potent payloads specifically to the diseased cells. AIT’s pipeline includes TCRLs directed to different disease indications. AIT also established a robust and proprietary technology for identification and validation of novel MHC-based targets. AIT was founded in 2006 by Prof. Yoram Reiter, Head of the Laboratory of Molecular Immunology at the Technion, Israel Institute of Technology, and Mira Peled-Kamar, Ph.D., AIT Chief Executive Officer. AIT is located in Haifa, Israel.

About Adicet Bio, Inc.

Adicet Bio, Inc. is a privately held, pre-clinical stage biotechnology company engaged in the design and development of cutting-edge immunotherapies for cancer and other disease indications, with a focus on novel universal immune cell therapies (uICT).  Adicet Bio is located in Menlo Park, California.

# # #


Aya Jakobovits, Ph.D.
President and Chief Executive Officer
Adicet Bio, Inc.
Tel 310.990.3832

For Media:

Joan Kureczka
Kureczka/Martin Associates
Tel 415.821.2413
Mobile 415.690.0210





ATI Management

Mira Peled-Kamar, PhD – Chief Executive Officer

Dr. Peled-Kamar, AIT’s Co-Founder and CEO, has extensive academic and biotech research experience in basic sciences as well as biotechnology and biomedical devices. Dr. Peled has worked for leading Israeli biotech companies including Biotechnology General and Interpharm, was the Co-Founder and CEO of BioMimic Pharma, and has been involved in the establishment of a number of start-ups. Dr. Peled received her PhD in Biochemistry and Molecular Biology from the Weizmann Institute of Science and completed her post doctorate at the University of California, Berkeley.
Yoram Reiter, PhD – Chief Scientific Officer

AIT Co-Founder and CSO, Professor Reiter is a world leader in the isolation of human TCRL molecules. Head of the Laboratory of Molecular Immunology at the Technion Institute, Prof. Reiter established a cutting-edge research program in the molecular immunology of cancer. His major work involves the development of novel immunotherapeutic approaches, as well as the study of molecular mechanisms in anti-tumor and anti-viral immunity. Prof. Reiter received his PhD from the Department of Immunology at the Weizmann Institute and subsequently spent 5 years at the NCI Laboratory of Molecular Biology headed by Dr. Ira Pastan, where he developed new approaches in antibody engineering. Prof. Reiter has published over 100 scientific papers and reviews, and holds 15 patents. He currently serves as an advisor to several pharmaceutical and biotechnology companies.

Galit Denkberg, PhD – R&D Manager

Dr. Denkberg leads AIT’s TCRL development team. A  graduate of the Technion’s Faculty of Biology, she worked with Prof. Yoram Reiter on the design and construction of the single-chain MHC molecules and was the first in the group to isolate TCRL antibodies from both immunized and naïve phage-display libraries. Through the years Dr. Denkberg has mastered a variety of molecular immunology, cellular immunology and molecular biology techniques and has become an expert in design, application, and characterization of TCRL antibodies. Dr. Denkberg is the author of 16 scientific papers related to the TCRL technology in leading peer-reviewed journals.



Read Full Post »