The Engineered T-Cell Receptor in Fusion Proteins, Antibodies & Cells: Emerging Opportunities for the Biopharmaceutical Industry -

Published: October 2013 | Pages: 84 | Format: PDF  

A comparative analysis and assessment of TCR technologies, pipelines and companies from an industry perspective

Therapeutic monoclonal antibodies have become an increasingly successful treatment modality with sales of US$ 65 bln in the year 2012 and with an average (continuous) annual growth rate from 2006 to 2012 of 18.9%. While antibody technologies are steadily evolving, the spectrum of druggable targets for monoclonal antibodies has remained limited to extracellular antigens, albeit including proteins, carbohydrates and glycolipids.

Access to druggable, IP-protected and validated new targets is a major bottleneck in the biopharmaceutical industry. Technologies which can deliver both new targets and the corresponding treatment modality, can expect significant financial acknowledgement.

The T-cell receptor (TCR) has recently emerged as a means to target peptide antigens derived from intracellular proteins, however, in a major histocompatibility complex (MHC)-restricted manner. The first companies have overcome significant technical hurdles in putting together a library of viable new TCR-targeted antigens and establish the corresponding standardized protein- and cell-based therapeutic frameworks.

This report entitled „The Engineered T-Cell Receptor in Fusion Proteins, Antibodies & Cells: Emerging Opportunities for the Biopharmaceutical Industry“ published in Ocotber 2013 describes chances and pitfals in exploiting the opportunities which offers the engineered T-cell receptor as integral part of fusion proteins, antibodies and cellular products. The key success factors are highlighted, the technical challenges described and solutions presented.

Benefits from the report:


Identify players in the field, from industry and academia;  

Find out which TCR technologies are valued by Big Pharma and Biotech;  

Understand the value of intracellular antigens targeted by the TCR;  

Recognize the challenges of TCR-based therapeutics and their solutions;   

Learn which TCR-based therapeutics are attractive for partnering;   

Find out which TCR therapeutic approaches are not yet tapped.  



Table of Contents  


0.         List of Abbreviations  


1.         Executive Summary  


2.         Introduction  


3.         The T-Cell Receptor  


4.         TCR Fusion Proteins  

4.1 Altor Bioscience  

4.1.1 Overview  

4.1.2 Financing history  

4.1.3 IP protection  

4.1.4 Partnering  

4.1.5 STAR technology  

4.1.6 Binding affinity of scTCRs  

4.1.7 Manufacturing of STAR molecules  

4.1.8 Targets for scTCRs  

4.1.9 Generation of scTCRs  

4.1.10 Other applications of STAR molecules  

4.1.11 STAR pipeline  

4.1.12 ALT-801 Preclinical characterization of ALT-801 Clinical results of studies with ALT-801 Ongoing clinical studies with ALT-801 Safety of ALT-801 in clinical studies Clinical immunogenicity of ALT-801 Clinical pharmacokinetics of ALT-801  

4.1.13 ALT-802  

4.1.14 Assessment  


4.2 Immunocore  

4.2.1 Corporate development of Immunocore  

4.2.2 Stability and solubility of TCRs  

4.2.3 Affinity of monoclonal TCRs (mTCR)  

4.2.4 Effector function for mTCR  

4.2.5 Target discovery for mTCRs  

4.2.6 Preclinical experience with mTCRs  

4.2.7 ImmTAC clinical lead program  

4.2.8 Partnering  

4.2.9 Assessment  


5.         TCR-Like (TCRL) Antibodies  

5.1 Eureka Therapeutics & Memorial Sloan-Kettering Cancer Center  

5.1.1 Target of TCRL antibody  

5.1.2 Generation of TCRL antibody  

5.1.3 Preclinical characterization of TCRL antibody  

5.1.4 Intellectual property  

5.1.5 Corporate background  

5.1.6 Assessment  


5.2 Applied Immune Technologies  

5.2.1 Corporate background  

5.2.2 Financial history  

5.2.3 Cancer target  

5.2.4 Technologies  

5.2.5 Viral targets  

5.2.6 Generation of TCRL antibodies  

5.2.7 Assessment  


6.         TCR-Transfected T-Cells  

6.1 Adaptimmune  

6.1.1 Corporate Background  

6.1.2 Overview of manufacturing  

6.1.3 The TCR engineering process  

6.1.4 TCR-transfected T-cells versus CAR-transfected T-clls  

6.1.5 Clinical R&D in cancer  

6.1.5 Clinical HIV study with TCR T-cells  

6.1.6 Assessment  


6.2       Academic Studies with TCR-Transfected T-Cells  


7.         „Artificial“ TCR T-Cells: Chimeric Antigen Receptor (CAR) T-Cells  

7.1 CAR-modified T-cells for cancer  

7.1.1 Background  

7.1.2 Clinical experience with CAR-modified T-cells  

7.1.3 The three generations of CAR-Modified T-cells  

7.1.4 Assessment  


7.2 Autologous CAR-Modified T-Cells  

7.2.1 Novartis & The University of Pennsylvania  

7.2.2 Celgene & bluebird bio & Baylor College of Medicine  

7.2.3 Kite Pharma  


7.3 Allogeneic CAR-Modified T-Cells  

7.3.1 Cellectis  


7.4 CAR-Modified Induced Pluripotent Stem Cells  


8.         Tumor-Infiltrating Lymphocytes (TILs)  

8.1 Lion Biotechnologies  


9.         Opportunity Analysis for TCR-based Products and Technologies  


10.       References  


11.       Corporate R&D Pipelines  


11.1 Adaptimmune  

11.2 Altor Bioscience  

11.3 Immunocore  

11.4 Lion Biotechnologies  


Tables in the Text  

Table 1     Financing history of Altor Bioscience  

Table 2     Financing history of Immunocore  

Table 3     Affinity enhancement of TCRs by Immuncore technology  

Table 4     Comparison of TCR T-Cells with CAR T-Cells  

Table 5     Investigator sponsored clinical studies with TCR