Immune cell directed therapies

At Boehringer Ingelheim, we have made a generational commitment to transforming cancer care, with the ultimate goal of curing a range of cancers. We are investigating cancer cell directed therapies that target key cancer drivers and hallmarks to directly kill cancer cells. In parallel, with immune cell directed therapies we are exploring new ways of directing and boosting the immune system against cancer cells. We consider that it is the smart combination of these approaches that could offer the greatest benefit for people living with cancer.

Immune Cell-Directed Therapies: training the immune system to recognize and attack cancer

Clinical research has shown that the current wave of therapies that restore the immune system function is beneficial in those patients with the so called ‘hot’ tumors, whose immune cells already recognize mutated antigens presented by cancer cells. However, such therapies have limited efficacy in tumor types that are not effectively recognized by our immune cells, commonly known as ‘cold’ tumors. We are developing complementary platforms, such as T-cell engagers, targeted cytokines, oncolytic viruses, cancer vaccines or tumor-infiltrating bacteria, which have the potential to turn ‘cold’ tumors ‘hot’, extending the benefits of immunotherapy to more patients.

Research topics in immune cell directed therapies:

Cancer vaccines & oncolytic viruses

AMAL Therapeutics developed a protein-based immunization technology platform (named KISIMA®), which is self-adjuvanting and enables the assembly within one chimeric fusion protein essential to generate potent immunity. Priming with KISIMA vaccine and a boost with a viral vector carrying both the same tumor antigens have the potential to reduce the risk of tumor relapse and metastasis by boosting memory immunity. This approach is currently in phase I clinical trial.

Oncolytic virus therapy is a cancer treatment approach that uses a virus that infects and breaks down cancer cells, while not harming healthy cells. Tumor antigens that are normally hidden from the immune system inside the cells are released, triggering an immune response to fight the tumor. The main oncolytic virus platform developed by ViraTherapeutics is based on VSV-GP (Vesicular Stomatitis Virus (VSV) glycoprotein (GP)) and is currently in clinical trial phase I.

Another key collaboration was established with Enara Bio to identify novel cancer antigens, leveraging Enara Bio’s Dark Antigen Platform Technology (EDAPT™). Several promising tumor antigens resulting from this fruitful partnership were recently in-licensed. Furthermore, with 3T Biosciences, we combine our patient-derived T-cell receptor (TCR) data to fuel 3T’s target discovery efforts to identify cognate antigens using its 3T TRACE (T-Cell Receptor Antigen and Cross-Reactivity Engine) discovery platform.

"We're a team of motivated scientists with the common goal to bring new medicines to patients."

Dr. Paul Adam. Head of Research Site Vienna.

"Our scientific ecosystem is truly remarkable, as it fosters the development of new therapeutic approaches."

Dr. Laetitia Devy-Dimanche. CEO AMAL Therapeutics.

"Blood, sweat, tears, but also fun at work, are key ingredients of all our drug candidates."

Dr. Lisa Egerer. Managing Director ViraTherapeutics.

T-cell engaging (TcE) antibodies:

TcE antibodies can re-direct cytotoxic immune cells specifically to cancer cells resulting in the selective killing of tumor cells. We developed a novel Immunoglobin G (IgG)-like bispecific T-cell engager designed to bind concomitantly to DLL3 on tumor cells and CD3 on T-cells. By creating a physical link between T-cells and tumor cells, the T-cell engager can activate T-cells against DLL3-expressing tumor cells, potentially resulting in their destruction. Activated T-cells can indirectly stimulate other immune cells to broaden the immune response against the tumor tissue. Our DLL3/CD3 T-cell engager is currently being evaluated for several indications in a clinical trial phase II.

Tumor-targeting bacteria

T3 Pharma develops a cancer therapy platform by harnessing the potential of live bacteria (Yersinia enterocolitica). The genetically engineered bacteria lack key virulence factors resulting in their selective accumulation in solid tumors and rapid clearance from healthy tissues. Furthermore, natural bacterial secretion systems can be used to inject selected proteins into target cells or the extracellular space. Hence, the platform can be used to deliver therapeutic proteins specifically within the tumor microenvironment. Our most advanced program is currently in clinical trial phase I.

Research areas supporting our therapeutic modalities

Proteins specifically located on the surface of cancer cells can be recognized by immune cells to trigger an anti-tumor immune response while sparing healthy tissue. The Cancer Antigen Discovery team supports Boehringer Ingelheim’s cancer vaccine and T cell engager pipelines by leading the discovery of novel cancer-specific targets. Furthermore, advanced human assay systems modeling the patients’ tumor tissues are urgently needed to understand the mechanisms of our drugs. Our human complex in vitro or ex vivo assay systems can be tailored for each project depending on the therapeutic target and the mechanism. These models range from more artificial tumor cell line-based 3D spheroids co-cultured with immune cells to more original precision-cut tumor slice cultures (PCTSC).

"We're excited to work with Boehringer and continue the development of our platform to treat cancer."

Dr. Simon Ittig. CEO T3 Pharmaceuticals AG.

"It's exciting to partner with top biotechnology companies to find novel tumor antigens."

Dr. Ralf Leonhardt. Scientific Director Discovery Research.

"We're building novel human tumor models to understand how immune therapies work:"

Dr. Iñigo Tirapu. Scientific Director. Discovery Research.

Collaboration is key

The work of our cancer immunology experts is complemented by collaborations with academic organizations and partnerships with biotech companies. We believe that by working together we can learn more, do more and achieve more to accelerate the delivery of much-needed new treatments for patients. In the field of TcE, we have been collaborating with Oxford BioTherapeutics to identify tumor-specific surface antigens by membrane proteomics. This successful collaboration has already resulted in a clinical program for neuroendocrine carcinomas.

Another key collaboration was established with Enara Bio to identify novel cancer antigens, leveraging Enara Bio’s Dark Antigen Platform Technology (EDAPT™). Several promising tumor antigens resulting from this fruitful partnership were recently in-licensed. Furthermore, with 3T Biosciences, we combine our patient-derived T-cell receptor (TCR) data to fuel 3T’s target discovery efforts to identify cognate antigens using its 3T TRACE (T-Cell Receptor Antigen and Cross-Reactivity Engine) discovery platform.

_Credits_:_Anna_{Bachmayr-Heyda}_,_Alvaro_{Ingles-Prieto (editorial)}

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