You know, it’s true -- there’s no place like home (especially Antibody Solutions’ new home in Santa Clara, California). At the same time, though, I probably would have stayed another week in Boston had there been a third conference that was as chock full of engaging presentations, intriguing research and useful data (plus some very stimulating hallway conversations) as the two back-to-back conferences I attended earlier this month: CAR-TCR Summit 2019 and Discovery on Target 2019.
In this post, I’ll summarize some of the highlights our team gleaned from the CAR-TCR Summit. Stretching over two days, the main conference brought together more than a thousand scientists and industry thought leaders who focus on CAR-T and TCR-based therapies. The conference kick-off was an Industry Leader Fireside Chat that included a musical segue chosen by each speaker (e.g., Chariots of Fire). It has only been two years since the first two therapies, Kymriah and Yescarta, were approved for B-cell lymphoma. In many ways, I thought the issues discussed were comparable to those raised for therapeutic antibodies in the mid-1990s. Thus, this is a highly exciting but also highly challenging time to be working in CAR-T research.
One key difference is that the regulatory path to approval of CAR-Ts is simpler, and regulatory agencies have been supportive of CAR-T therapy studies. However, the challenges and unknowns are significant. These include:
Understanding tumor microenvironments and what are the appropriate targets
Understanding variability in patients and what factors can improve response
Improving the potency of CAR-Ts
Demonstration of efficacy against solid tumors
Addressing safety concerns of caregivers
Effectiveness and safety of autologous (e.g., patient) versus allogeneic (e.g., stem cell) derived therapies
Efficacy of CAR-T vs. CAR therapies
Commercial innovations to lower the cost of manufacturing
The presentations and panel discussions covered a wide array of topics, including:
Comparisons of autologous and allogeneic therapy
Next-generation strategies to overcome the tumor microenvironment and enhance persistence
Development of antibody-TCR expressing T cells against solid and hematological malignancies
Yeast display technology to define peptide MHC complexes binding to a lead TCR
AlloEBV CAR-Ts and next-generation costimulation domains
Management strategies to mitigate toxicity and minimize risk of impact on therapeutic efficacy
Some of the most intriguing takeaways we brought back from the Summit included these findings:
BCMA appears to be the next target to be approved. It has shown 11.8 months durability in patients.
Hypoxic conditions in tumors change the functional activity of CAR-T cells.
The level of MHC Class 1 expressed on the surface of some tumors decreases as the tumor ages, and CD3 may be a limiting factor as the introduced TCR must be shared with existing TCR. Further, high-affinity TCR may not be the most effective since a lower-affinity TCR may cross over to more than one TCR (cytokine release syndrome is less for TCR than CAR).
The use of an anti-CD19CAR mRNA can enhance NK cell cytotoxicity against B-cell malignancies.
Alloimmune Defense Receptors (ADR) selectively recognize and eliminate alloreactive lymphocytes, which spares resting cells. In addition, ADRs enable CAR-T cells to resist T- and NK-cell rejection both in vitro and in vivo, and CAR-T cells co-expressing ADR are protected from elimination and are more efficacious.
Off-the shelf CAR-T cells can be generated using a pluripotent cell platform.
In sum, we considered the CAR-TCR Summit a very worthwhile investment of our time and generally recommend this conference if you’re working in the CAR-T and TCR space. On a related note, we also believe that the insights and data we gathered at the Summit will help us better serve our clients as they expand the scope and methodologies of their CAR-T and TCR research. Leveraging the knowledge of the target, immunization strategies and the latest antibody and automation technologies are vital to identifying and delivering qualified antibody candidates with the required affinity to the tumor-associated antigen you’re targeting.
To learn more about how we can help advance your CAR-TCR research by generating fit-for-purpose antibodies and the associated nucleic acid sequences that can be used to recombinantly engineer CAR constructs with antigen binding domains, please contact us by phone at +1 650.938.4300 or +1 888.843.1069 (toll-free), or via email at inquiries@antibody.com.
And we invite you to review this post outlining CAR-T cell therapy and, in particular, the critical importance of having ready access to high-quality, expertly developed antibodies to CAR-T targets for your research.