Cambridge Healthtech Institute 第3回

Adoptive T-Cell Therapy

( 養子T細胞療法 )

改善されたアプローチによる研究段階から臨床段階への円滑な移行

2018年3月19-20日 | Hilton London Canary Wharf | ロンドン

 

このカンファレンスプログラムでは、養子T細胞療法のさまざまなアプローチを取り上げ、それぞれの制約と強み、オフターゲット毒性を回避しながら最適な特異性を実現する方法などについて考えます。会期中は、固形がんに対する治療法の開発と個別化医療以外の治療法での可能性、自動化と単純化のための取り組みなどをめぐって議論が展開され、研究段階から臨床試験段階へと至るプロジェクトでの前臨床モデル、トランスレーショナル研究、臨床試験の成功例などがデータを交えて紹介されます。

 

Final Agenda

3月19日 (月)

08:00 Registration & Morning Coffee

次世代の技術

09:00 Chairperson's Opening Remarks

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine  

 

 

09:10 KEYNOTE: ImmTAC® Reagents: Novel Bi-Functional TCR-Based Biologics for Targeted Immunotherapy

Bent Jakobsen, PhD, CSO, Immunocore

We have developed novel, bi-functional soluble T cell receptor (TCR) ImmTAC® (Immune mobilising monoclonal TCR against Cancer) which consists of an affinity-enhanced TCR linked to an anti-CD3 effector domain. ImmTAC molecules bind specific peptides presented on the cell surface by human leukocyte antigen, vastly increasing the number of potential targets. Our lead ImmTAC molecule, IMCgp100, is currently undergoing clinical trials for the treatment of advanced cutaneous and uveal melanoma. Additional ImmTAC molecules are in development for a variety of other cancers.

09:40 Development of the Next Generation of Chimeric Antigen Receptors (CARs) for the Treatment of Solid Tumors

Richard Morgan, PhD, Vice President, Immunotherapy, bluebird bio

Genetically-engineered CAR T cells are designed to supplement a patient's immune system and can be further engineered to survive and potentially to overcome immune evasion mechanisms employed by cancer cells. We found that addition of a PI3-kinase inhibitor during CAR T cell manufacture represented a facile method to enrich for memory-like CAR T cells. Combined with gene editing and synthetic biology, we hope to develop CAR T cell technology for use in the treatment of solid tumors.

10:10 Advances with Allogeneic Gene-Edited CAR-T Cells

Laurent Poirot, PhD, Head, Early Discovery, Innovation, Cellectis

T-cell adoptive immunotherapy emerges as a powerful approach in oncology. Cellectis technologies combined with 18 years of gene editing experience enable efficient and specific editing of any gene in primary cells and offer unparalleled possibilities for the next generation of immunotherapies. TALEN technology allows creation of non-alloreactive allogeneic CAR T-cells while also empowering cells with additional safety and efficacy attributes such as resistance to then tumour microenvironment and compatibility with standard of care.

10:40 Sponsored Presentation (Opportunity Available)

11:10 Networking Coffee Break

腫瘍浸潤リンパ球と非通常型T細胞

11:40 Next Generation Products Based on Tumour Infiltrating Lymphocytes

Robert Hawkins, MB BS, MRCP, PhD, FRCP, Cancer Research UK Professor, Medical Oncology, University of Manchester & Honorary Consultant, Medical Oncology, Christie Hospital

Tumour Infiltrating Lymphocytes (TIL) are a prognostic biomarker in many tumours and have therapeutic efficacy in many tumour types. They can be used in a variety of ways to evolve next generations products, e.g. to enhance efficacy and to improve survival and proliferation by introducing novel genes. TILs can provide a rich source of tumour specific TCRs which can be cloned for conventional TCR based gene therapy or TCR libraries to produce synthetic TIL.

12:10 The Advantages of Targeting Cancer with Unconventional T-Cells and T-Cell Receptors

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection and Immunity, Cardiff University School of Medicine

The major subsets of human T-cells target processed protein antigens presented as peptides bound to HLA at the cell surface. Our dissection of successful cancer immunotherapy and other pipelines has identified various broadly tumoricidal T-cell clones that are not HLA-restricted. These unconventional T-cells can kill most cancer types from all patients and thereby offer hope for pan-population, pan-cancer diagnostics and therapeutics.

12:40 Sponsored Presentation (Opportunity Available)

13:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:40 Session Break

予測バイオマーカー、特性評価、親和性最適化の利点

14:00 Chairperson's Remarks

Boris Engels, PhD, Senior Investigator, Exploratory Immuno-Oncology, Novartis, Inc.

 

 

 

14:05 Advances in CAR-T Therapy for Chronic Lymphocytic Leukemia (CLL)

J. Joseph Melenhorst, PhD, Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania

We have shown that CD19-specific chimeric antigen receptor (CAR) T cell therapy can induce durable remission in most patients with acute but not chronic lymphocytic leukemia (ALL and CLL). We have now identified markers predictive of response and identified key mechanisms of response in CLL. Our preclinical studies have informed next-generation CAR-T based therapies for CLL. Our current trial in CLL has trumped our highest expectations in terms of response rate.

14:35 Analytical Characterization Studies for CAR-T Cell Therapy

David G. Kugler, PhD, Senior Scientist, Team-Lead, T Cell Profiling, Juno Therapeutics, Inc.

Chimeric antigen receptor (CAR)-T cells are a promising new modality for cancer immunotherapy, and many variants are rapidly being developed across the immuno-oncology space for haematological and solid tumor malignancies. The field has displayed enormous promise; however, the rules governing which attributes drive efficacy are still being learned. Here, we present early insights from transcriptomic and epigenetic profiling of CAR-T cells describing how cell state may play an important role.

15:05 Taking TCR-Engineered Cells to the Clinic

Tom Holdich, MBBS, Head, Global Medical Affairs & EU Clinical Development, Clinical Research, Adaptimmune

Adoptive T-cell therapy is a novel approach to treatment that has demonstrated promising results but also presents unique challenges in development. Adaptimmune has developed Specific Peptide Engineered Antigen Receptor (SPEAR) T-cells with affinity-optimized TCRs that recognize intracellular cancer-expressed antigens. This requires target selection, TCR development, non-clinical safety testing and scalable manufacture. SPEAR T-cells targeting MAGE-A10, MAGE-A4, and AFP are in clinical trials in several solid tumor indications.

15:35 Networking Refreshment Break

革新的なアプローチ

16:05 Small Molecule Control of CAR-T Cells

Simon Thomas, PhD, MBioch, Associate Director, Immunobiology, R&D, Autobus Ltd.

CAR-T cells are autonomous and after infusion they engraft and expand; hence, unlike small molecular or protein therapeutics, they have no half-life. Toxicity can therefore be progressive and fulminant. We have developed a number of different strategies for "remote control" of CAR-T cell activity whereby CAR-T cells are engineered to respond to small molecule drugs. These different approaches will be described and contrasted.

16:35 Synthetic Biology: Minimizing Toxicity and Maximizing Efficacy with Adoptive T Cell Therapies

Peter Emtage, PhD, CSO, R&D, Cell Design Labs

We have developed technologies that provide novel cellular control mechanisms to reduce toxicities while maximizing efficacy. The Throttle switch and synNotch technologies enable control of intrinsic activity of the CAR T with a definable mechanism in the case of Throttle switch and a logic gated decision paradigm in the case of synNotch. Application of these systems in the clinic enables modulation of safety issues like CRS and on/off target toxicities while maximizing efficacy.

17:05 Problem Solving Roundtable Breakout Discussions

Table 1: Enhancement of Specificity and Efficacy of CAR-T Cells

Moderator: John Maher, FRCPath., PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King’s College London

Table 2: Potential of CAR-T Therapy for Solid Tumours

Moderator: Boris Engels, PhD, Senior Investigator, Exploratory Immuno-Oncology, Novartis, Inc.

Table 3: Analytical Characterization for CAR-T Cell Therapy

Moderator: David G. Kugler, PhD, Senior Scientist, Team-Lead, T Cell Profiling, Juno Therapeutics, Inc.

Table 4: Considerations for pre-clinical to clinical translation of CAR-T Cell Therapy

Moderator: Eric L. Smith, MD, PhD, Assistant Attending, Myeloma & Director, Clinical Translation, Cellular Therapeutics, Memorial Sloan Kettering Cancer Center

Table 5: Selection of Treatments to Combine with T Cell Therapy

Moderator: Reno Debets, PhD, Associate Professor, Tumor Immunology, Medical Oncology, Erasmus MC Cancer Institute

18:00 Welcome Reception in the Exhibit Hall with Poster Viewing

19:00 End of Day

3月20日 (火)

臨床現場における養子T細胞療法の進歩

08:00 Registration & Morning Coffee

08:30 Chairperson's Remarks

John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King's College London

 

 

 

08:35 Advancing CAR-T Cell Therapy to the Clinic

Eric L. Smith, MD, PhD, Assistant Attending, Myeloma & Director, Clinical Translation, Cellular Therapeutics, Memorial Sloan Kettering Cancer Center

CAR-T cell therapy has proved to have dramatic efficacy in relapsed/refractory B-ALL. In addition to CD19 targeted CAR-T cell therapy (B-ALL, CLL, NHL), we have developed and translated to the clinic CAR-T cell therapy products targeting PSMA (Prostate), Mesothelin (Lung, Breast), MUC16 (Ovarian), and most recently BCMA (Myeloma). Furthermore, we developed and translated novel ‘armored' CAR-T cell approaches including the co-expression of 4-1BBL (B-cell malignancies) or IL12 (Ovarian).

09:05 TCR-Engineered T Cells Combined with T Cell Co-Stimulation to Treat Solid Tumors

Reno Debets, PhD, Associate Professor, Tumor Immunology, Medical Oncology, Erasmus MC Cancer Institute

To ensure further clinical development of TCR gene therapy, it is necessary to accurately select TCRs and, at the same time, include strategies that restore or enhance accumulation and activation of T cells in tumor tissues. Here, we present our recent preclinical and translational studies to enhance TCR-engineered T cell therapy, its combination with T-cell co-stimulation, and preparations towards a clinical T cell therapy trial to treat patients with melanoma and head-and-neck cancer in 2018 Q2.

09:35 Design of a Highly Efficacious CAR Targeting Mesothelin in Solid Tumors

Boris Engels, PhD, Senior Investigator, Exploratory Immuno-Oncology, Novartis, Inc.

Following clinical experience with a murine scFv based CAR (SS1) targeting mesothelin (MSLN), we pursued the generation of a fully human MSLN-targeting CAR with increased potency against solid tumors. The strong anti-tumor activity of the lead CAR was confirmed in a unique primary pancreatic cancer xenograft mouse "clinical trial". The lead candidate is now being evaluated in a Phase I clinical study in patients with malignant mesothelioma, ovarian, and lung cancer.

10:05 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

固形腫瘍の標的化による臨床現場での治療法の進歩

11:15 Challenges of Targeting Solid Tumours with CAR-T Cells in the Clinical Setting

Fiona Thistlethwaite, MB, PhD, Consultant, Medical Oncology, The Christie NHS Foundation Trust

For solid malignancies, significant hurdles still need to be overcome if CAR-T cell therapy is to become a valid strategy in the clinical setting. These challenges include the identification of appropriate tumour antigens that avoid on-target/off-tissue toxicities, achieving adequate T-cell homing, and overcoming the immune suppressive tumour micro-environment. These aspects will be discussed in the context of CEA targeted CAR-T cell therapy for solid malignancies.

11:45 ErbB Targeted CAR-T Cell Immunotherapy of Head and Neck Cancer: T4 Immunotherapy

John Maher, FRCPath, PhD, Consultant & Senior Lecturer, Immunology, Cancer Studies, King's College London

T4 immunotherapy consists of a CD28+CD3z-based chimeric antigen receptor (CAR), targeted against the extended ErbB network, and which is co-expressed with an IL-4 responsive chimeric cytokine receptor. Preclinical efficacy and safety has been demonstrated in models of head and neck, ovarian, breast cancer and mesothelioma. Phase I clinical evaluation is now ongoing in patients with locally advanced or recurrent head and neck cancer, employing intra-tumoural delivery to minimize toxicity.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Close of Adoptive T-Cell Therapy