Innovative In Vivo Cell Therapies: A New Frontier in Cancer Treatment
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Chapter 1: Introduction to In Vivo Cell Therapies
In recent years, there has been a growing interest in the development of innovative in vivo cell therapies aimed at treating cancer and other diseases. Axial Discovery is at the forefront of this movement, partnering with visionary founders and inventors. We focus on investing in early-stage life sciences companies, often when they are merely concepts. Our dedication to supporting unique inventors who aspire to create lasting businesses is unwavering. If you or someone you know has an exciting idea in the life sciences sector, we would love to connect and potentially invest in your vision. Reach out to us at [email protected].
The potential to transform immune cells directly in the body presents a significant opportunity for cancer treatment. One challenge with CAR-T cell therapy is the diverse phenotypes of tumors, which can lead to some cancer cells evading detection by targeting receptors. By programming lymphocytes with chimeric antigen receptors (CARs) that can identify various tumor antigens, we could tackle this issue. However, creating a comprehensive range of T-cell variants using current ex vivo techniques is impractical. Alternatively, utilizing injectable agents to program T-cells in vivo could provide a swift method to induce immunity against any tumor antigen. The Mooney Lab at Harvard/Wyss Institute holds leading intellectual property in this area, enabling fine-tuning of multiple T-cell specificities to align with the unique antigenic profile of each patient's tumor. Additionally, in vivo therapies can mitigate supply chain complications and eliminate the need for preconditioning, which also benefits B-cell treatments.
Section 1.1: Key Components of In Vivo Cell Therapies
The essential components for effective in vivo cell therapies include:
- Delivery Vector: Options such as lentiviral vectors (as used by Umoja), nanoparticles, and HSVs. These must ensure safety, ease of manufacturing, and ideally, require a manageable number of doses.
- Payload: The actual therapeutic substance that is transformed into an immune cell, which must be effectively packaged into the delivery vector.
- Shared Biology: The likelihood of success increases over time across various payloads when using the same vector.
The two leading organizations in this arena are Interius Biotherapeutics, stemming from Saar Gill's Lab at Penn, and Umoja Biopharma, primarily based on Michael Jensen's research at Fred Hutch. Moreover, Yvonne Chen's Lab at UCLA is developing intellectual property for a new venture in this field, highlighting her exceptional contributions.
Subsection 1.1.1: Understanding T-Cell Exhaustion
An important aspect of cell therapies is identifying the active ingredients that can either activate or inhibit immune responses. Exhausted T-cells (Tex) are categorized into two primary types: progenitor and terminally differentiated. While often functional, Tex cells may reach a stalemate with either pathogens or cancer, presenting a unique opportunity for reversing this exhaustion. There is a pressing need to deepen our understanding of the distinct subsets of exhausted T cells, their diversity, and the underlying epigenetic factors.
T-cell exhaustion is characterized by several features, including the progressive loss of effector functions, sustained upregulation of inhibitory receptors, altered expression of key transcription factors, metabolic changes, and an inability to revert to a quiescent state. These aspects represent significant opportunities for designing novel cell therapies.
For instance, Lyell is leveraging c-Jun overexpression from the Mackall Lab at Stanford to counteract T-cell exhaustion. Their cell therapy recently received IND clearance for treating solid tumors, marking an exciting advancement worth monitoring.
Section 1.2: Noteworthy Research and Case Studies
Current research in the field includes:
- Intellectual property from the Poojary Lab focused on deleting Cbl-b to reverse T-cell exhaustion.
- The Wherry Lab's discovery of the transcription factor TOX as a mediator of T-cell exhaustion.
- The Oldstone Lab at Scripps is engaged in small molecule screening to identify ways to reverse T-cell exhaustion.
A compelling study from the Wherry Lab explored whether exhausted CD8+ T-cells (Tex) could regain normal functions after eliminating chronic antigenic stimulation. This research used the LCMV mouse virus to induce T-cell exhaustion and found that while most Texs perished after being transplanted into non-infected mice, a few that survived showed some recovery in gene expression profiles akin to normal memory T-cells, albeit remaining exhausted with stable epigenetic modifications.
This research serves as a foundation for understanding T-cell exhaustion and discovering new strategies to reverse it. For in vivo therapies, such data is crucial for designing treatments that can effectively combat tumor evasion and leverage the potential of transforming immune cells in situ, thereby broadening the range of treatable conditions with potentially curative therapies.
Chapter 2: The Call for Innovation in Cell Therapies
We are actively seeking talented individuals across various disciplines, including inventors, operators, product managers, and engineers. The field of cell therapies needs fresh perspectives focused on new platforms and scalable business models. Axial is prepared to provide investment as well as access to our extensive network of founders, executives, and venture partners. We are particularly enthusiastic about the potential of epigenetic reprogramming to convert Texs into effector/memory T-cells in vivo. If this aligns with your interests, please reach out to us at [email protected].
The first video showcases the journey of Saar Gill in the realm of CAR-T cell therapies, providing insights into the current advancements and future possibilities in this transformative field.
The second video features Dr. Andrew Scharenberg discussing in vivo CAR T-cell therapeutics, highlighting significant breakthroughs and the ongoing efforts at Umoja Biopharma.