Small molecule AVM0703 rapidly induces activation and mobilization of NKT-like cells expressing both gdTCR and invTCR (AVM_NKT). Anti-tumor effects are rapid, including activity against CNS tumors and extranodal lymphoma, disease sites associated with poor outcome to standard therapy, including CAR T cells. Preclinically, activity has been demonstrated against autoreactive T/B cells, immune-resistant lymphoma, xenografted human T-ALL, melanoma, and multiple myeloma. AVM0703 is also effective as neoadjuvant before chemoimmunotherapy or cell transplant.

ICT01, an anti-BTN3A mAb, selectively activates ?9d2 T cells resulting in remodeling of the tumor microenvironment. However, the pharmacodynamic effects of ICT01 are dependent on the number of circulating gamma9d2 T cells, which is low in most advanced cancer patients. Preclinical studies showed that ICT01 plus IL-2 induces selective expansion of gamma9d2 T cells with minimal Treg expansion supporting an ongoing Phase I/IIa (EVICTION-2) in patients with advanced-stage solid tumors.

• Use of gene editing technology
• Engineering of gamma delta-based TCRs
• Creation of gamma delta fusion constructs​

The role of gamma delta T cells in the control of AML after allogeneic hematopoietic cell transplantation will be presented. Advances in large-scale artificial antigen-presenting cell-based ex vivo expansion of gamma delta cells for clinical use will be discussed. Study design and early results of the Phase 1 trial of donor γδ T cell infusion for treatment of adverse risk AML after allogeneic transplantation will also be covered.

Conventional gamma/delta-T cell expansion relies on indirect technologies such as zoledronic acid. The lack of direct control over expansion results in high manufacturing variability, and low-scale. PhosphoGam direct expansion using synthetic phosphoantigens enables nanomolar control, consistent quality and 50,000x more efficient expansion than zoledronic acid.

SUPLEXA therapeutic cells represent a novel approach to adoptive cellular therapy involving the activation, differentiation, and expansion of peripheral blood mononuclear cells to broadly target cancer while sparing normal tissues. 

• An autologous cellular therapy comprised of multiple immune cell types including NK, NK-T, gd T cells, and ab CTL
• Ongoing Phase 1 clinical trial safety and efficacy update
• Summary of exploratory longitudinal PBMC and plasma analyses from treated patients suggests a potential approach to pharmacodynamic monitoring of SUPLEXA cell activity
• The absence of drug-related adverse events facilitates future single-agent dose optimization efforts and plans for combination studies.

We have developed a manufacturing technology in which peripheral blood-derived gamma delta T cells are expanded in the presence of TGF-beta, enhancing yield and intrinsic anti-tumour activity of these cells. In this presentation, we will demonstrate the utility of these cells as effectors of anti-tumour immunity and present mechanistic insight into the unique attributes of these cells.

Cellular starting materials are critical components to produce Cell Therapies. Amongst others, the appropriate donor, starting material specifications, procurement and logistics play a major role regarding the quality of the starting material and therefore can directly impact the success of the manufacturing process. All the above need to be considered to achieve high consistency, despite the challenge of the intrinsic biological donor-to-donor variability when using primary cellular material.

Allogeneic gamma delta (Gd) T cells bear promises for developing off-the-shelf T cell therapies for cancer through leveraging their unique functional attributes. Gd T cell therapy development requires precise balancing between anti-tumor armoring and cloaking against the patient's immune cells. Immatics is building on its expertise in TCR-based tumor targeting and adoptive T cell therapies to develop such product candidates via our proprietary ACTallo platform through data-driven gene engineering and highly optimized manufacturing.

LAVA Therapeutics’ Gammabody platform is designed to engage Vgamma9Vdelta2 T cells for selective tumor cell killing, while non-transformed cells expressing the target are spared. Two programs, one in hematology and one in solid cancer, have progressed to clinical development. The presentation will address the lead candidate selection as well as our progress to the clinic.

As many cell therapy companies work to bring allogeneic cell therapies into reality there are a few pioneers utilizing a lesser-known T cell sub-type called gamma delta cells as their approach of choice. This talk will cover the different types of allogeneic approaches and why Luminary believes that gamma delta cells will shine in comparison to other methods.

Neuroblastoma (NB) is the most common cancer in infants and represents approximately 15% of cancer-related deaths. We initiated a Phase I study using allogeneic ex vivo expanded gamma delta (?d) T cells for relapsed NB (NCT05400603), and have extended the ?d T cell platform to include proprietary cell-specific transgene expression vector designs and gene transfer systems for eBite expression, which generate our Allogeneic Donor Expanded and Programmed T (ADEPT) cells.

ImmTAC molecules are TCR-anti CD3 bispecific fusion proteins that can redirect and activate polyclonal T cells to kill tumors in an MHC-restricted manner, representing a novel class of anti-cancer drugs with activity in solid tumors. To overcome the limitations of MHC restriction, we are expanding the ImmTAC platform to gd TCRs targeting monomorphic unconventional antigen presenting molecules. The challenges of targeting non-peptidic ligands will be discussed, alongside our current understanding of the ImmTACs mechanism of action.

We are developing next-generation antibodies, such as Fc-engineered antibodies with enhanced immune function or antibody-drug conjugates (ADCs), for the treatment of breast cancer. Our lab has developed a novel ADC against triple-negative breast cancer (TNBC) which greatly restricts growth of human TNBC xenograft tumours in vivo. We have also engineered novel Fc-enhanced antibodies against HER2-positive breast cancer and TNBC which induce significantly greater direct cell killing by antibody-dependent NK cell-mediated cytotoxicity (ADCC) and reprogramming of macrophages towards a more pro-inflammatory, anti-tumoural phenotype.