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

Published By :

La Merie Publishing

Published Date : Oct 2013

Category :

Biotechnology

No. of Pages : 84 Pages

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 Content


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

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 
4.1.12.1  Preclinical characterization of ALT-801 
4.1.12.2  Clinical results of studies with ALT-801 
4.1.12.3  Ongoing clinical studies with ALT-801 
4.1.12.4  Safety of ALT-801 in clinical studies 
4.1.12.5  Clinical immunogenicity of ALT-801 
4.1.12.6  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 

List of Table


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  

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