Exploring T-cells in cancer
The immune system is a magnificent design. One of its many superpowers is the ability to detect and destroy cancer cells. Our goal is to harness that potential by investigating therapeutic modalities, such as so-called ‘T-cell engagers’ (TCEs), to stimulate the immune response against hard-to-treat cancers. At Boehringer Ingelheim, we have made a generational commitment to transforming cancer care.
Thymus-derived lymphocytes, or T-cells, are key members of the immune system. They are highly specialized to identify and kill infected and abnormal cells that could pose a threat to the body. However, cancer cells can develop strategies to escape the immune system and continue to multiply. Eventually this can lead to a lack of T-cells within tumors, characterizing them as “cold” tumors.
Our commitment to immuno-oncology
We are exploring ways of directing and boosting the immune system against cancer cells and investing in multiple platform technologies to potentially deliver meaningful advances in areas of high unmet patient need.
T-cell engagers are promising targeted immunotherapeutics, which could reactivate T-cells, potentially resulting in the selective killing of cancer cells by the body’s own immune system.
Lamine Mbow, Global Head of Cancer Immunology and Immune Modulation at Boehringer Ingelheim, shares our approach to immuno-oncology, highlighting our investigational T-cell engagers platform and how we are driving innovation in this space.
About DLL3-positive tumors
Delta-like ligand 3 (DLL3) is a protein that has been found to be highly expressed on the cell surface of up to 85% of small cell lung cancer (SCLC) tumors and approximately 77% of other neuroendocrine carcinomas (NECs).1,2 In normal tissues, DLL3 is minimally expressed, making it a potential therapeutic target.
SCLC is the most aggressive subtype of lung cancer and represents about 13% of all lung cancer cases worldwide. NECs are highly aggressive cancers occurring in multiple organs, including the gastrointestinal tract, skin, bone, prostate and pericardium.3,4 There is an urgent need for additional targeted immunotherapeutics for people living with SCLC and NEC.
We are investigating an Immunoglobin G (IgG)-like bispecific T-cell engager designed to bind concomitantly to DLL3 on tumor cells and CD3 on T-cells.5 By creating a physical link between T-cells and tumor cells, the T-cell engager could potentially activate T-cells against DLL3-expressing tumor cells, potentially resulting in their destruction by the body’s own immune system. Activated T-cells could indirectly stimulate other immune cells to broaden the immune response against the tumor tissue. Our investigational DLL3/CD3 T-cell engager is currently being evaluated clinically for the treatment of people living with extensive stage SCLC (ES-SCLC) and extrapulmonary neuroendocrine carcinoma (epNEC).
As of November 2023, The U.S. FDA granted BI 764532 with:
- Fast Track Designation in advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC-Lung) expressing DLL3 whose disease has progressed following at least one prior line of treatment including platinum-based chemotherapy.
- Fast Track Designations in ES-SCLC with disease progression following at least two prior lines of treatment including platinum-based chemotherapy, and for epNEC with advanced or metastatic disease following at least one prior line of treatment including platinum-based chemotherapy.
- Orphan Drug Designation for SCLC.
This compound is an investigational agent and has not been approved for use by any regulatory authority, including the U.S. Food and Drug Administration (FDA). The efficacy and safety of this investigational compound has not been established.
Together we can change lives
Our purpose is to transform lives for future generations. Our curiosity, creativity and passion for science lead us to take the paths scientifically less travelled and the courage to face challenging journeys as we relentlessly pursue cancer research. This is only possible with the support of our exceptional people and global family of partners, who share the same passion for science and enjoy working together to deliver breakthroughs.
References
1. Puca, L. et al. Sci. Transl. Med. 11, (2019).
2. Rojo, F. et al. Lung Cancer 147, 237–243 (2020).
3. Caliman, E. et al. Lung Cancer 175, 88–100 (2023).
4. Raphael, M. et. Al. CMAJ. 2017 Mar 13; 189(10): E398–E404.
5. Hallet, J. et. al. 2015 Feb 15;121(4):589-97. doi: 10.1002/cncr.29099. Epub 2014 Oct 13.