第2回年次

Next-Generation Immunotherapies
(次世代免疫原性)

新たなin vivo療法での免疫システムのリプログラミング

2023年5月18〜19日 EDT(東部夏時間)

Cambridge Healthtech Instituteの「次世代免疫療法」カンファレンスでは、オンコロジー、免疫障害、希少障害への次世代の免疫療法を推進する新たなモダリティとエンジニアリング技術を考察します。トピックにはin vivoエンジニアリング、mRNA、ウイルスベクター、LNPを介したCAR Tやその他のカーゴのデリバリー、ガンマ・デルタ、IPSC、B細胞といった細胞治療への既製のアロジェニックアプローチといったエキサイティングな分野が含まれます。

5月14日(日)

- 5:00 pm Main Conference Registration1:00 pm

Recommended Pre-Conference Short Course2:00 pm

SC2: Introduction to Lipid Nanoparticle Characterization and Formulation

*Separate registration required. See short courses page for details.

5月16日(火)

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.

5月18日(木)

Registration and Morning Coffee7:30 am

THE ERA OF IN VIVO CELL ENGINEERING AND DELIVERY
in vivo細胞エンジニアリングとデリバリーの時代

8:25 am

Chairperson's Remarks

Christian J. Buchholz, PhD, Professor & Head, Molecular Biotechnology & Gene Therapy, Paul Ehrlich Institut

8:30 am KEYNOTE PRESENTATION:

In vivo Engineering Considering Probability of Technical, Regulatory, and Commercial Success

Nicholas A. Boyle, PhD, CEO, Abintus Bio

In vivo genetic medicines are poised to disrupt a range of therapeutic areas.  The ideal product profile for these agents include: 1) Safety and tolerability with intravenous administration and flexibility for repeat dosing; 2) Gene delivery to target cells using an off-the-shelf, standardized vehicle; and 3) Scalable manufacturing of purified product with low immunogenicity. Building on lessons learned, this presentation will address approaches to mitigate technical, regulatory, and commercial risks to improve probability of success and deliver on the promise of in vivo engineering, and improve patient outcomes and access, including those in underserved communities.

9:00 am

Engineering Retargeted Fusogens for in vivo Gene Delivery to T Cells

Kutlu G. Elpek, PhD, Senior Director, Sana Biotechnology

Effectively addressing cell-specific delivery has an opportunity to improve the therapeutic potential of in vivo gene therapies. We have developed a novel platform for engineering fusogens to target cellular molecules of choice, thereby enabling in vivo cell-specific delivery across many cell types with a fusogen-directed gene therapy vector. In vivo generation of CAR T cells, using gene therapy vectors with T cell targeting fusogens for in vivo CAR delivery, show promise in preclinical models and may provide broader access to CAR therapies.

9:30 am Solve the riddle of your lentiviral titer with Leprechaun

Alex Shephard, PhD, Product Manager, Leprechaun, Unchained Labs

Monitoring lentiviral titer, structural stability and non-viral contamination throughout production is critical to generating high yield, high purity therapeutics. Leprechaun is the only tool that helps solve your lentiviral riddle by dishing out the lentiviral titer and percentage of capsid-containing virus from crude and pure samples, while providing information on viral aggregation, soluble p24 and non-viral EV contaminants. Get a comprehensive lowdown on your lentivirus throughout your entire production process.

Coffee Break in the Exhibit Hall with Poster Viewing10:00 am

10:40 am

Surface Engineered Gene Vectors for in vivo CAR T Cell Generation

Christian J. Buchholz, PhD, Professor & Head, Molecular Biotechnology & Gene Therapy, Paul Ehrlich Institut

Highly effective, yet complex to manufacture, simplifying CAR T cell generation is at the forefront of current research. Generating CAR T cells in vivo will heavily rely on vector technology, particularly high selectivity for T lymphocytes. Using surface-engineered lentiviral vectors targeted to T cell markers we have provided proof-of-concept for this strategy in humanized mouse models. As an alternative to lentiviral vectors, AAV vectors can be targeted to CD8+ T lymphocytes through insertion of CD8-specific DARPins into exposed loop regions. Ongoing preclinical studies are evaluating the different vector platforms and will identify potential hurdles to be solved toward clinical application.

11:10 am

In vivo Production of Functional CAR T Cells by mRNA Targeted Lipid Nanoparticle

Haig Aghajanian, PhD, Co-Founder and Vice President of Research, Capstan Therapeutics

Using targeted lipid nanoparticles (tLNP), we were able to transiently reprogram T cells in vivo by delivering modified mRNA encoding a CAR against fibroblast activation protein (FAP). This treatment resulted in the reduction of cardiac fibrosis and the restoration of cardiac function. The ability to produce transient, functional CAR T cells in vivo with mRNA addresses some of the biggest hurdles in cell therapy including manufacturing, scalability, and safety concerns.

11:40 am

CAR T Cells Manufactured Rapidly in situ Using Virally Activated Endogenous APC

Larry R. Pease, PhD, Professor, Biochemistry & Molecular Biology & Immunology, Mayo Clinic & Foundation

Current CAR T cell manufacturing uses artificial ligands to induce activated T cells that are functionally distinct from T cells activated in their natural settings in vivo. In situ CAR T cells are generated directly in immune-reactive lymph nodes in just 3 days from T cells responding to virus-encoded MHC alloantigens presented by endogenous APC. Following in vivo retargeting with viruses encoding chimeric antigen receptors, the resulting in situ CAR T cells are capable of targeting antigen-positive cells systemically in the blood and in a solid tumor setting.

Luncheon in the Exhibit Hall and Last Chance for Poster Viewing12:10 pm

CELLULAR REPROGRAMMING, INCREASING SPECIFICITY
細胞の初期化、特異性の向上

1:15 pm

Chairperson's Remarks

Nicholas A. Boyle, PhD, CEO, Abintus Bio

1:20 pm

Synthetic Biology Platforms for Biomedical and Biotechnology Applications

Lior Nissim, PhD, Assistant Professor & Principal Investigator, Synthetic Biology Lab, Hebrew Univ Jerusalem

Cell-state specific gene expression is a major challenge in biomedicine and biotechnology. Our synthetic biology platforms limit the expression of any encodable genetic outputs only to cell states or tissue types of interest. We can rapidly and efficiently identify synthetic promoters that demonstrate superior specificity compared to native ones. Our synthetic gene circuits integrate the activity of multiple synthetic promoters via Boolean logical gates and generate output only when a predetermined promoter activity pattern is detected. This approach enhances gene expression specificity and efficacy. Our technologies are modular and could be adapted to target virtually any cell state.

1:50 pm

In situ CAR Therapy Using oRNA

Amy M Becker, PhD, Director, Immunology, Orna Therapeutics

We have developed a novel, synthetic, circular coding RNA platform (oRNA technology) which exhibits significant improvements in production, expression, and formulation compared to mRNAs. Given the successes as well as remaining challenges with CAR T cell therapies, we combined our oRNA technology with novel immunotropic LNPs to create an off-the-shelf “autologous” in situ CAR (isCAR) therapy that effectively delivers anti-CD19 CAR to immune cells and regresses tumors in a human-PBMC-engrafted tumor-bearing mouse model. oRNA-enabled isCAR therapies promise a transient, re-dosable, and scalable immune cell therapy without requiring lymphodepletion for the treatment of cancer. 

2:20 pm Increasing Target Specificity and Tackling Intracellular Targets with Keyway’s TCRm Discovery Offering

Dongxing Zha, PhD, CTO TCR Discovery & Engineering at Alloy Therapeutics, CEO Keyway TCR Discovery, Alloy Therapeutics

TCR mimics (TCRm) are promising formats for reaching intracellular targets for next-generation immuno-therapies. Keyway’s TCRm Discovery offering comprises industry-leading solutions, including high-quality pMHC complex antigen production capabilities and proprietary specificity screening. A case study featuring a discovery campaign with this offering yielded highly specific, functional TCRm binders against an intracellular immuno-oncology target, with downstream functional screening results of TCRm-based CAR

Networking Refreshment Break2:50 pm

3:20 pm

In vivo Reprogramming of CAR T Cells Using Targeted LNPs

Viktor Lemgart, Research Fellow, Tidal Therapeutics, a Sanofi Company

Ex vivo CAR T cell therapies have proven successful in the clinic, but their broad application is still facing significant challenges due to the elaborate and expensive engineering and manufacturing of T cells. Tidal Therapeutics has developed a new technology that allows the generation of CAR T cells directly in vivo. The technology uses mRNA, formulated in lipid nanoparticles that are specifically targeted to circulating T cells to transiently express CARs on the surface.

COMMERCIALIZING IN VIVO ENGINEERED CELL THERAPIES
in vivoでの改変細胞療法の商業化

3:50 pm PANEL DISCUSSION:

Promise or Reality? - Delivery Platforms Shaping the Future of in vivo Engineering

PANEL MODERATOR:

Nicholas A. Boyle, PhD, CEO, Abintus Bio

  • What are the major strengths and weaknesses of your chosen gene delivery system(s) and how well does that match with the original reasons for choosing it?
  • How are you mitigating technical, regulatory, and commercial risks?
  • What product profiles will best serve patient need? 
  • How are key stakeholders such as FDA, payers, investors, and clinicians viewing the promise of in vivo genetic medicines?
  • How does your delivery system address key challenges associated with manufacturing, re-administration, and pre-existing immunity?
PANELISTS:

Philip R. Johnson, MD, CEO, Interius Biotherapeutics

Andy Murphy, PhD, VP, Early Research, Kriya Therapeutics

Haig Aghajanian, PhD, Co-Founder and Vice President of Research, Capstan Therapeutics

Close of Day4:30 pm

5月19日(金)

Registration Open7:00 am

INTERACTIVE DISCUSSIONS
インタラクティブディスカッション

7:30 amInteractive Discussions with Continental Breakfast

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.

LOGIC GATES, ADVANCES IN CELLULAR ENGINEERING AND IN VIVO DELIVERY
論理回路、細胞エンジニアリングとin vivoデリバリーの進展

8:25 am

Chairperson's Remarks

Samuel Lai, PhD, Professor, Pharmacoengineering & Molecular Pharmaceutics, University of North Carolina at Chapel Hill

8:30 am

Tuning the T Cell Synapse for Logic-Gated CAR Behavior

Timothy Riley, PhD, Senior Scientist, A2 Biotherapeutics

Logic-gated, two receptor systems amplify many of the challenges associated with CAR design. Here, we leverage concepts from the kinetic segregation model to design a tuneable CAR platform (Tmod) for optimal T cell activation and inhibition. Furthermore, by rationally integrating structural differences between activator and blocker targets, the Tmod platform is broadly applicable to a wide variety of therapeutic indications.

9:00 am

Viral Vectors for in vivo Engineering of B and T Cells

Samuel Lai, PhD, Professor, Pharmacoengineering & Molecular Pharmaceutics, University of North Carolina at Chapel Hill

A platform that can selectively transduce specific immune cells in vivo can enable a range of personalized cellular and biologics immunotherapy. Towards this goal, our group has employed various principles from molecular biology and pharmaceutics to engineer different viral vector systems that can selectively transduce B and T cells in vivo with exceptional fidelity and potency. We will present both published and unpublished data.

9:30 am

In vivo Programming with MT-302

Thomas E. Prod'homme, PhD, Vice President, Translational Research, Myeloid Therapeutics

Myeloid's novel in vivo engineering platform specifically targets and activates myeloid cells to elicit broader anti-tumor adaptive immunity. Through this approach, Myeloid demonstrates that delivery of lipid-nanoparticles (LNPs) encapsulating mRNA results in selective uptake and expression by myeloid cells in vivo, leading to potent tumor killing in multiple cold tumor models. These data demonstrate the potential for Myeloid's technology to program cells directly in vivo.

10:00 am Singularity mice: a novel genetic platform for developing single domain antibodies and multi-specific antibodies

Weisheng Chen, PhD, Founder and CEO, Leveragen, Inc.

Using gene editing and targeted replacement technologies, we have extensively modified the mouse IgH allele to produce murine or human heavy chain antibodies only, but none of the conventional antibodies (IgM/IgD/IgG/IgE/IgA). The resulting Singularity Musculus and Singularity Sapiens mice exhibit normal B cell developmental profiles, mount robust immune response upon immunization, and have been deployed to develop single domain antibodies with superior affinity and biophysical properties.

Networking Coffee Break10:30 am

11:00 am

Bispecific RNA Nanoparticles Carrying Ligands to Bridge Cancer Cells and T Cells in Therapy

Peixuan Guo, PhD, Fellow of the National Academy of Inventors, Sylvan G. Frank Professor & Endowed Chair, Pharmaceutics, Ohio State University

We have constructed many bispecific-RNA nanoparticles harboring ligands, aptamers, cell-binging chemical drugs, or Immune-checkpoint-targeting molecules to bind receptors of T cells or cancer cells. RNA's ability to form various 3D configurations allows the creation of bispecific RNA nanoparticles carrying various ligands to bridge cancer cells and T cells in therapy (Shu & Guo. Stoichiometry of multi-specific immune checkpoint RNA Abs for T cell activation and tumor inhibition using ultra-stable RNA nanoparticles. Mol Ther Nucleic Acids. 2021:24:426).

11:30 am

Engineering Viral Vectors for Gene Delivery to Antigen-Specific T Cells

Ellen Xu, Graduate Student, Birnbaum Lab, MIT

Selective transduction of cell populations has the potential to unlock a new generation of therapies. We recently developed a novel pseudotyping strategy in which VSVGmut, an affinity-ablated version of the VSVG, is coexpressed with a targeting protein to enable cell-type specific infection. Incorporating a peptide-MHC targeting protein enables antigen-specific infection of T cells, allowing us to pair pMHCs with cognate TCRs and to set the stage for cell-specific gene therapy. 

Presentation to be Announced12:00 pm

Close of Next-Generation Immunotherapies Conference12:30 pm

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