• Recent technological advances have made concepts like tumor vaccines or transgenic TCRs more promising than ever. Can myeloid cell therapies perform similarly with reduced labor and cost?
• What have we learned thus far about the practical limitations of generating myeloid-based cell therapies? What has succeeded?
• Considering the successes of CAR Ts or T-cell directed therapies, how should we approach the idea of myeloid based cell therapies? Competitor or teammate?

• Exploring how integrative and naturopathic oncology can support patients undergoing advanced immune therapies such as CAR T-cell, bispecific antibodies, NK cell vaccines, and dendritic cell therapy
• Clinical applications for monitoring immune therapy response and toxicity using biomarkers and interleukin profiling (e.g., IL-6, IL-8, IL-1β, VEGF, MMP9, TNF-α) from a patient-centered lens
• Practical strategies for managing treatment-related adverse events (cytokine release syndrome, neurotoxicity, fatigue) through evidence-informed supportive care 
• Shared decision-making models to align complex therapies with patient values and quality-of-life goals 
• Real-world insights into harmonizing conventional protocols with integrative care to improve outcomes and experience

Candel Therapeutics' enLIGHTEN platform uses HSV-based gene constructs to precisely modify solid tumor microenvironments. Combining oncolytic viruses with personalized gene payloads, enLIGHTEN leverages human biology and data-driven design. This unique approach allows tunable immunotherapies, aiming to personalize tumor modulation for improved therapeutic outcomes.

Dendritic cell therapy double loading is an advanced immunotherapy approach for cancer that enhances dendritic cells' ability to stimulate anti-tumor immune responses. This method involves loading dendritic cells with two types of tumor antigens: one to prime a broad immune response and another to target specific tumor markers. By activating both innate and adaptive immunity, double loading improves efficacy in combating cancers, especially in overcoming tumor immune evasion.

Adoptive T cell transfer is effective for hematologic malignancies but struggles with solid tumors due to inadequate infiltration of vascularly administered T cells at tumor sites. The E-selectin/sialyl Lewis X (sLeX) interaction is crucial for leukocyte extravasation. We demonstrate that enforced sLeX display on antigen-specific T cells can be achieved by FUT6-mediated exofucosylation or Golgi-fucosylation. However, only exofucosylation enhances tumor infiltration, significantly improving therapy efficacy in murine cancer models, including solid tumors and metastases. Therefore, exofucosylation offers a promising strategy to enhance adoptive T cell therapy for solid and metastatic cancers.

HLA-G is normally expressed in the placenta to direct immune tolerance but is derepressed in about 50% of leukemias and solid tumors to direct immune evasion. NKILT has developed Chimeric ILT Receptor technology (CIR) to specifically target HLA-G. Further, proprietary activation mechanisms drive potent and persistent cytotoxicity in natural killer cells.  CIR NK cells have strong potential as an allogeneic, off-the-shelf therapy against a wide range of cancer indications.

• Case presentation of a patient who received dual immune checkpoint inhibition for a locally advanced MSI-H gastric cancer and achieved a pathologic complete response with neoadjuvant immunotherapy alone but developed a grade 5 immune-related adverse event that complicated curative intent surgery and ultimately led to his death. 
• Discussion of the therapeutic promise of immunotherapy as well as a need for non-operative protocols in patients who have likely achieved a complete response
  
• Updates in nonoperative management of mismatch repair-deficient tumors 

Next-generation CAR T cells endowed with multiple enhancements could overcome the numerous challenges for treating solid tumors but will require the introduction of multiple genetic modules that often exceed the cargo capacity of a single vector. However, multi-vector engineering results in a heterogeneous, poorly-defined cell product. Here we report on STASH-Select, a simple platform technology for purifying cells containing multiple genetic modifications using a single-step selection compatible with GMP workflows.

CAR T cell therapies remain unsuccessful in treating solid tumors due to the hostile tumor microenvironment (TME). OUTLAST conditioning exposes CAR T cells to TME-like conditions ex vivo for superior function against solid tumors. OUTLAST CAR T cells show superior efficacy and durability in vivo in aggressive tumor rechallenge models. OUTLAST anti-CD70 CAR Ts are currently under evaluation in a Phase 1 clinical trial for ccRCC. OTX conditioning is simple and can improve CAR T manufacturing processes. OTX cells have unique transcriptional and metabolic profiles, allowing for enhanced persistence. OTX CAR T cells show superior clearance of secondary tumor challenges than conventionally generated CAR Ts.

Key challenges in the CAR T field for solid tumors include limited persistence and off-target effects. ArsenalBio leverages synthetic biology to enhance both the specificity and potency of CAR T cells. ArsenalBio’s logic-gated technology enables CAR T cells to selectively respond based on the presence of two tumor antigens, minimizing off-target activity on healthy cells. CAR T cells are also engineered to contain Synthetic Pathway Activators (SPA) and shRNAs that improve persistence and survival in the immunosuppressive tumor microenvironment. ArsenalBio’s approach has the potential to improve CAR T cell efficacy and safety in solid tumors, expanding treatment options for patients with limited alternatives.

Most cancer drivers are intracellular where they are inaccessible to conventional CAR T cells. We have developed tools for identifying tumor-specific molecules presented on HLA and targeting them using peptide-centric (PC)-CAR T cells. These therapies demonstrate potent preclinical efficacy and are entering the clinic in 2025.