Technology

Overview

Overview

Our goal is to revolutionize cancer therapy on a global basis by developing TCR T-cell therapies (called SPEAR T-cells) with the potential to treat a wide range of cancer types and patients.

Our TCR T-cell therapies have advantages over other immune therapies and cancer therapies. The video below provides more information.

About Our SPEAR T-cells

Our TCR T-cell therapies have advantages over other immune therapies and cancer therapies.

Our SPEAR T-cell video below provides more information.


Our TCR T-cell therapies are capable of recognizing peptide fragments from both proteins present inside the cell and expressed on the outside of the cell. We can, therefore, target a large number of proteins. 

More targets, inside the cancer cell and out, means more options for targeting these cancers.

Our T-cell therapies are all subjected to a meticulous pre-screening package which aims to minimize any chance that our T-cell therapies might bind to peptides other than the intended target cancer peptide. 

Better specificity, we believe, improves the safety profile of our T-cell therapies.

Our T-cell therapies have general applicability to a wide range of cancer types, many of which currently have low patient survival rates.

The foundation of our TCR therapies is the work we did with NY-ESO SPEAR T-cells, which we transitioned to GSK in 2018, showing responses in two solid tumors and treating more than 90 patients in six different indications. 

Read below to find out more information about each of our 3 products and the cancer types that they are targeting.

ADP-A2M10 (MAGE-A10)

Urothelial (bladder), Melanoma, Head and Neck, Non-Small Cell Lung Cancer (NSCLC)

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ADP-A2M4 (MAGE-A4)

Urothelial (bladder), Melanoma, Ovarian, Non-Small Cell Lung Cancer (NSCLC), Esophageal, Gastric, Synovial Sarcoma, Myxoid/Round Cell Liposarcoma (MRCLS), Head and Neck

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ADP-A2AFP (AFP)

Hepatocellular (liver) cancer 

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We enhance the body's natural systems by affinity engineering naturally occurring T-cell receptors (TCRs) to recognize and bind to specific cancer peptides.

In addition to our clinical pipeline, we have a large pipeline of identified and validated targets against which we can direct new T-cell therapies.

We believe that our SPEAR T-cell therapies may one day be capable of treating patients who have limited, if any, treatments available.

The Immune System

The immune system plays an important role in targeting and destroying diseased and abnormal cells.

There are two modes of action by which the body's immune system can target and destroy diseased or abnormal cells. 

  • The first uses an antibody recognition system, which targets whole proteins on the cell surface;
  • The other is through T-cell receptors that target peptides presented on the Human Leukocyte Antigen complex, or HLA. 

The HLA peptide complex presents peptides that are derived from intracellular target proteins. TCRs target and bind to a specific HLA peptide complex, resulting in the targeting and destruction of the relevant cell. 

Unfortunately binding of naturally occurring T-cell receptors to cancer targets tend to be very poor because cancer proteins appear very similar to naturally occurring proteins and are very good at evading the immune system. T-cell receptors that recognize "self-proteins" are eliminated during early human development. 

At Adaptimmune, we harness the immune system and use engineered T-cell receptors to fight back against cancer. The affinity enhanced T-cell receptors, unlike their natural counterparts, can recognize and bind to cancer cells and as a result, can stimulate the immune system to target and destroy cancer cells.

Cancer Cell

Our Engineered T-cells Therapies

Affinity Enhancement: The Science of Engineering a Proprietary TCR Therapeutic to Increase Tumor Specificity.

Naturally occurring T-cell receptors struggle to recognize cancer proteins. This is because the cancer proteins appear very similar to other proteins within the body, "self-proteins". At Adaptimmune, we have a unique ability to engineer the affinity of the T-cell receptors so that they can recognize cancer proteins and as a result can detect and fight cancer within patients.

T-cell receptors consist of two associated protein chains: the alpha (α) and beta (β) chains. Each of the chains has two regions: a variable region and a constant region. The constant region sits next to the T-cell membrane and the variable region of the two chains binds to the target peptides. The variable region of each TCR chain has three hypervariable complementarity determining regions or CDRs. Our technology modifies these CDRs in order to enhance affinity to the cancer cell's HLA peptide complex.

By engineering the sequences that encode the T-cell receptors within a T-cell we can generate a T-cell therapy which works with a patient's own immune system to target specific cancer peptides. Our technology platform allows us to identify and select the T-cell receptors which are likely to prove the most effective in patients whilst minimizing off-target (non-cancer cell) binding.

Our Technology Platform

Adaptimmune has an industry-leading technology platform which enables identification of targets, engineering and selection of T-cell receptors to targets and the preclinical screening of our end T-cell therapies. Our technology platform gives us a unique ability to drive T-cell therapies forward to the clinic whilst minimizing the risk of cross-reactivity to healthy and non-target tissue. The platform has been developed over 15 years by leading experts in immune-oncology and T-cell receptors.


Our scientists work meticulously to maximize the potency and specificity of all of our SPEAR TCR therapeutics and screen them to minimize the risk of cross-reactivity to healthy and non-target tissue. This integrated and proprietary technology platform has been developed over more than 10 years by leading experts in the field of T-cell based therapeutics.

Our proprietary identification system provides target peptides specifically expressed in tumors and not in normal tissue. This process includes (a) analysis of presentation of the relevant target peptides in cancer cells; (b) screening for presentation of the relevant target peptide in healthy tissue to ensure minimal risk of cross-reactivity; (c) validation of presentation on the cancer cell surface.

Once the target peptide has been identified and validated, we can generate an engineered TCR therapeutic candidate from natural TCRs. Our internal process includes:

  • Rapid identification and cloning of TCRs, deriving engineered TCRs capable of binding to any selected target cancer peptide;
  • Development of multiple stable, soluble engineered TCRs using our proprietary disulfide bond methodology;
  • Utilization of a proprietary phage display system to select engineered TCRs with maximum potency and specificity from a large, diversified library.

We have developed a proprietary preclinical screening program that seeks to minimize any potential off-target binding or cross-reactivity, with a key goal of improving the safety profile of our product candidates while maximizing their potency. Our proprietary preclinical screening program is split into the following stages:

  • Molecular analysis to systematically identify peptides within the human body that are similar to the target cancer peptide and which therefore might be bound by the affinity-enhanced engineered TCR;
  • Human cell testing to assess whether the affinity-enhanced engineered TCR binds to samples of normal cells and whole blood samples.

Intellectual Property

We have composition of matter patents and patent applications covering all of our T-cell therapies including our ADP-A2M10 (MAGE-A10), ADP-A2M4 (MAGE-A4) and ADP-A2AFP (AFP) T-cell therapies.

Manufacturing

Our manufacturing process allows us to enhance the body’s natural immune defenses to target solid tumors by optimizing the binding of T-cells and their receptors. This allows the body to recognize the cancer cells and remove them from the body.

Our Manufacturing Process

Publications

Our clinical trials and products are featured in notable publications.

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