- 5:00 pm Main Conference Registration1:00 pm
Recommended Pre-Conference Short Course2:00 pm
SC3: In silico and Machine Learning Tools for Antibody Design and Developability Predictions
*Separate registration required. See short courses page for details.
Dessert Break in the Exhibit Hall with Poster Viewing1:40 pm
ENGINEERING SMARTER CAR T THERAPIES
Towards In Vivo Engineering of the Immune System
Ex vivo CAR-engineered T cells showed remarkable clinical efficacy, especially in a subset of patients with B cell malignancies. Nevertheless, hurdles related to access, manufacturing, and performance across broader disease categories warrant development of novel therapeutic platforms. In vivo precision engineering of the immune system utilizing synthetic nano-formulations may overcome both logistical and mechanistic limitations thereby potentially expanding the footprint of immunotherapy within oncology and beyond.
Synthetic Immune Receptors and Signalling
Programmed and highly targeted activity of cell therapies has the potential to both reduce toxicity and concentrate the therapeutic effect where it is most needed, improving safety and efficacy. Our mission is to engineer and distribute a comprehensive toolkit of clinically optimized technologies for cell-based therapeutics, so we can make an impact across diseases with high unmet needs.
By directly addressing key synthesis bottlenecks in their discovery cycles, researchers can now rapidly evaluate candidate immunotherapy biologics at speeds previously unattainable.
Come learn how Telesis Bio’s BioXp® solutions heave enabled:
- Optimization of CAR generation workflows, and the assembly of optimized CARs.
- Generation of mRNA for T cell manipulation, enabling rapid candidate screening through transient modulation of cellular phenotypes.
- Automated overnight synthesis of lead candidates across biologics discovery workflows
Refreshment Break in the Exhibit Hall with Poster Viewing3:50 pm
Synthetic Immune Receptor (SIR), a Next-Generation CAR Platform
Despite the success with CAR T cells in hematologic malignancies, there are several limitations to this approach including toxicities, CAR T cell exhaustion, and lack of persistence. To overcome the above design limitations of the current generation CAR T constructs, we have generated a next-generation CAR T platform designated Synthetic Immune Receptor (SIR) that provides physiological TCR-like signaling and overcomes most of the limitations of current generation CAR constructs.
CAR T Cells Targeting Tumor Glycosylation and TME
Chimeric antigen receptor T cells are genetically modified lymphocytes conventionally re-targeted towards specific macromolecules defined by the variable domains of monoclonal antibodies. Most CAR T cell therapies have been developed to target cell-surface protein antigens; however, antibody-based re-targeting expands the repertoire of macromolecules T cells can target, including carbohydrate-based antigens. Here, we demonstrate that truncated O-glycoforms of tumor-associated antigens are a class of actionable immune targets for CAR T cells.
Disinhibition of Early CAR T Cell Activation via CD5 Knockout Enhances the Anti-Tumor Activity of Adoptive T Cell Therapies against Cancer
One of the main barriers to the effective activity of adoptively transferred T cells is their inhibition when they reach the tumor bed. In this study, we discovered that CD5 inhibits CAR T activation and that the knockout (KO) of CD5 using CRISPR-Cas9 enhances the anti-tumor effect of CAR and TCR T cells in multiple hematological and solid cancer models.
Close of Day6:00 pm
Dinner Short Course Registration6:00 pm
Recommended Dinner Short Course6:30 pm
SC8: CAR T Cells: Improving Safety While Retaining Therapeutic Activity
*Separate registration required. See short courses page for details.
Registration and Morning Coffee7:30 am
TARGETING SOLID TUMORS
Overcoming Suppression of NK Cells in the Tumor Microenvironment
NK cell immunotherapy is a promising approach for cancer treatment, with low risk of graft versus host disease and adverse effects. One of the major hurdles of this approach is the immune suppressive tumor-microenvironment. In our work, we applied unbiased large-scale CRISPR screens on both the tumors and the NKs, to identify mechanisms of tumor cell resistance to NKs, for improved NK cell immunotherapies.
Engineering NK Cells for Improved Immunotherapy
One challenge of CAR T cell therapy is tumor relapse due to loss of target antigen on tumor cells or poor persistence of CAR T cells in patients. To overcome this challenge, we have developed CARs that recognize peptide-MHC where the peptides are derived from oncogenic mutations. Arming cytokine-induced memory-like NK cells, which can persist in patients for months, with tumor-specific CARs may lead to better long-term efficacy of CAR-NK cell therapies.
NK Cell Engineering for Enhanced Targeting of Advanced Solid Tumors
We described human memory-like NK cells with enhanced anti-tumor activity. We have recently demonstrated the safety and promising activity of using memory-like NK cells in AML and MDS. In my talk, I will describe key properties of the memory-like NK cells; summarize the preclinical development of the CAR-armed memory-like NK cells in ovarian and pancreatic cancer, and describe early clinical results and correlative labs from our ongoing clinical trial of cytokine-engineered allogeneic NK cells in combination with CTL4 blockade in patients with advanced head and neck cancer.
While cell therapy is different from traditional large molecule or small molecule therapies, similar mathematical modeling principles can be applied to cell based programs to provide guidance on target selection, lead optimization and clinical study design, etc. In this talk, I will demonstrate how mathematical models describing cell dynamics, cell distribution, target expression and binding affinity can be used to support quantitative decision making for CAR-T or CAR-NK programs.
Coffee Break in the Exhibit Hall with Poster Viewing10:30 am
Transition to Plenary Keynote Session11:10 am
PLENARY KEYNOTE SESSION
Advancing Innovative Biologics Modalities from Research to Clinical Application - Novel Platforms, Automation, and Computation
Addressing disease biology in the clinic with protein therapeutics has become increasingly complex. Turning to innovative and novel scaffolds offers opportunities to tailor therapeutics not previously possible due to advances in host cell engineering and protein design approaches. Designing and developing these modalities requires a next-generation approach as we exploit increased potential design space and also growing data sources to leverage as we invent the next wave of therapeutics.
YOUNG SCIENTIST KEYNOTE
Engineering Prime Editor Proteins for Therapeutic Applications
Precision gene editing technologies have the potential to address a wide range of genetic diseases. Prime Editing is a recently developed “search-and-replace” gene editing approach that can precisely perform a wide variety of DNA sequence edits at programmed target sites in human genomes without requiring double-strand DNA breaks or donor DNA templates. I will describe advances to prime editing technology that improve its efficiency, specificity, and capabilities for therapeutic applications.
Session Break1:00 pm
JAX developed a novel PBMC humanized mouse model to assess de-risk CAR-T-cell immunotherapy. The model allows assessing CAR-T efficacy and expansion, cytokine release syndrome, and downstream toxicity altogether in the same mouse. In addition, the model can distinguish a distinct CAR-T response against different tumor types and tumor burdens. The platform can be used to assess the individual difference in both autologous and allogeneic CAR-T treatment.
To expedite antibody-based drug development, DIMABio developed more than 5000 on-shelf lead antibody molecules on 300 druggable targets with its DimAb® single B platform. In this presentation, we will elaborate DimAb® platform and showcase how we developed anti-GPRC5D CAR T-cell therapy constructs from leads to IIT clinical trial stage with our collaborator. The preliminary data from ongoing clinical trial exhibits astonishing clinical efficacy on RRMM patients.
Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussions page on the conference website for a complete listing of topics and descriptions.
TABLE 4: Commercializing Cell and Gene Therapies - IN-PERSON ONLY
SOLID TUMORS AND IMPROVING TARGETING
Advances in CAR-M Cellular Immunotherapy
Adoptive cell therapies have demonstrated remarkable outcomes in hematologic malignancies, but efficacy in solid tumors is still lacking. We have established a novel, proprietary monocyte and macrophage-based cell therapy platform based on chimeric antigen receptor macrophages (CAR-M).
Novel Solid Tumor Targets and Technologies to Increase Potency in the Pipeline
This talk will feature novel targets for CAR T therapy that are relevant in several prevalent cancer types, and strategies of advanced CAR T engineering and combination therapy to augment potency and facilitate clinical implementation.
Current assays to ensure efficacy and predict in-vivo performance are insufficient as only 1 in 8 immunotherapeutic candidates receive approval.
We will review high impact journals highlighting how cell avidity has proven to be:
• A quick in-vitro assay with robust correlation to in-vivo
• Positively rank and negatively cull candidates in the same assay
• Reduce time and expense to murine studies while increasing confidence in lead selection
Ice Cream Break in the Exhibit Hall with Poster Viewing4:35 pm
PEGS BOSTON COMMON: SPEED NETWORKING
How Many New Contacts Can you Make? - IN-PERSON ONLY
Bring yourself, your business cards or e-cards, and be prepared to share and summarize the key elements of your research in a minute. PEGS-Boston will provide a location, timer, and fellow attendees to facilitate the introductions.
Off-the-Shelf Allogeneic EBV CAR T Cells
Allogeneic T cells have qualities that make them an ideal platform for treating disease. Evolution of CAR T designs and next-generation armoring technologies to overcome the hostile tumor microenvironment will be explored, including the promise of a platform that doesn’t require HLA or TCR gene editing and safety, expansion, and persistence implications.
dAb vs scFv in CAR
Despite the recent approval of CARVYKTI, historically scFv has been the preferred binding format in CAR T cell therapies. Single domain antibodies (dAb), however, display several favorable biophysical characteristics such as smaller size, increased paratope diversity, and improved stability. Here we compare a set of 20 affinity and domain-matched dAb and scFv-based CARs, evaluate their biophysical properties, and compare their functionality head-to-head to assess which format may prevail.
Novel Protein Engineering Concepts to Improve the Safety and Specificity of CAR T Cells
Major limitations in the CAR field include the poor controllability of CAR T cells after administration in vivo and their limited tumor specificity. To address these important challenges, we have engineered protein-based switches for CAR T cell regulation with an orally available and non-toxic small molecule drug. In addition, we have generated avidity-controlled CARs (AvidCARs) for combinatorial antigen recognition and small molecule-mediated CAR T cell control in vivo.
Networking Reception in the Exhibit Hall with Poster Viewing6:40 pm
PEGS BOSTON COMMON: WOMEN IN SCIENCE MEET UP
Women In Science Meet Up - IN-PERSON ONLY
The Women in Science Meet Up celebrates women trailblazers who are setting their own course in science. We invite women and men to come celebrate the successes of these women in breaking down barriers and inspiring future generations of female leaders. Come join fellow scientists and share your personal and professional journey.
- Who or What inspires you to explore a career in science?
- What fuels your imagination and spirit when you’re faced with challenges?
- What is your proudest moment?
- What can each of us do to improve things further?
Close of Cell-Based Immunotherapy Conference7:40 pm