On May 10, 2021 Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, today presents new data on components of its preclinical programs targeting the development of future T cell receptor-modified T cell (TCR-T) therapies against solid cancers at the 18th Annual Meeting of the Association for Cancer Immunotherapy (CIMT) (Free CIMT Whitepaper) taking place on 10-12 May 2021 (Press release, MediGene, MAY 10, 2021, View Source [SID1234579498]). The three eTalk presentations can be found on Medigene’s website: View Source
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Component 1: Proprietary new T cell receptors (TCRs) targeting novel tumor-specific antigens that are potential solid cancer TCR-T therapy target candidates
Identifying novel tumor-specific antigens (TSAs) as targets for T cells is a vital goal in the development of effective and safe cancer immunotherapies. As Medigene has recently disclosed, ten novel tumor-specific peptides stemming from non-coding regions of the genome of tumor cells have been identified that can be recognized by TCRs. These "immunogenic" peptides were present in tumors from several patients with solid cancers of different origin (including ovarian, breast, and lung cancer), but were not detected in healthy tissues in work performed in collaboration with the University of Montréal.
To date, Medigene has isolated more than 20 TCRs of T cell clones that recognize these novel TSAs and have the potential to become next-generation TCR-T therapy candidates. Their functional and safety characterization is ongoing, as presented in the current eTalk.
Component 2: Medigene’s inducible TCR (iM-TCR) – A fine control system to switch TCR-T cells on and off
The iM-TCR system could allow physicians to avoid unwanted side effects of TCR-T therapy or to fine-tune an ongoing immune reaction. This is part of Medigene’s work on the safety and functionality of engineered T cells for adoptive transfer into patients.
The iM-TCR system controls the level of expression of an introduced TCR on the surface of T cells, thereby governing the amount of functional activity of the TCR-T cells on the cell surface. In the presence of the appropriate drug the TCRs which contain the iM-TCR signature are brought onto the T cell surface; without the drug, they are down-regulated from the surface and new TCRs are only replaced upon new specific drug induction. The presence or absence of the drug therefore determines the level of activity of the TCR-T cells, potentially giving clinicians the possibility of switching on and switching off TCR-T activity as required.
Medigene’s scientists show in the eTalk that iM-TCR-expressing cells can be tightly controlled by the dose and timing of drug-induced expression, allowing fine control of TCR-T cell activity.
Component 3: TCR-4 + PD1-41BB switch receptor – Enhanced killing of solid tumor specimens
Solid tumors grow stealthily, hiding from the immune system and evading T cell attacks, using mechanisms such as the expression of the checkpoint molecule PD-L1 on their surface. Medigene has developed the PD1-41BB switch receptor, turning the tumors’ off-signal sent by PD-L1 into an activation signal for its TCR-T cells.
In the eTalk Medigene’s scientists illustrate that adding the PD1-41BB receptor to TCR-T cells enhances their metabolic fitness and their killing of tumor cells, as demonstrated using TCR-4, Medigene’s lead TCR candidate against solid tumors. TCR-4 is a non-mutated TCR isolated from a healthy donor that, in the context of HLA-A2, specifically recognizes a peptide stemming from the PRAME protein. TCR-T cells expressing only TCR-4 have already demonstrated potent preclinical in vitro and in vivo efficacy. Adding the PD1-41BB switch receptor further improves cell killing functions and metabolic fitness of the TCR-Ts without inducing off-target toxicities.
Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: "Our high-throughput functional T cell screening platform efficiently identifies T cells and their TCRs against a wide variety of potential target antigens. The identification of novel TSAs from non-coding regions of the genome adds to the range of cancer antigens that Medigene can use as targets for these immunotherapies. We can also limit the risk of off-tumor reactivity of tumor-specific TCR-T cells through tight control of TCR surface expression using our iM-TCR system. Importantly, we believe tools such as our PD1-41BB switch receptor will allow our TCR-T cells to overcome tumor evasion from immune attacks without giving rise to potential side effects as seen, for example, when using systemic PD-1/-L1 blocking agents.
We are excited that the phenomenal progress of our technology programs is advancing our TCR-T therapies towards solid cancer indications. Our approaches could improve clinical safety and efficacy in TCR-T therapies against Medigene’s unique tumor-specific targets."