aDC1 vaccine / Roswell Park, University of Pittsburgh - LARVOL DELTA

A proposed convergent molecular chain linking senescence, cancer, and chronic infection to a correctable failure of dendritic cell instruction. (PubMed, Front Immunol) - "If the chain is correct, α-DC1 administration should restore endogenous IRF8 expression, re-enable cDC1 surveillance, and decelerate biological aging as measured by DunedinPACE. We outline the mechanism, testable predictions, and falsification criteria."

Journal • Review • Infectious Disease • Oncology • DNMT1 • IL12A • IRF8 • STAT3

A phase 2 study of intravenous pembrolizumab and intratumorally injected autologous dendritic cells (DCs) in refractory colorectal cancer (CRC). (ASCO-GI 2025) - P2 | "Eligible patients must have prior treatment with, or contraindication to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF, and anti-EGFR therapy (if RAS wild type), be anti-PD-1/PD-L1 therapy naïve, have ECOG PS ≤1, and have at least two target lesions, one amendable to biopsy and injection...A Simon two-stage Optimal design will enroll 9 patients in stage 1, and if ≥1 response occurs, 8 more patients will be added in stage 2. If ≥3 responses are observed, the treatment will be deemed promising for further study."

P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • CD8 • FOXP3 • IL12A • MSI

Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Roswell Park Cancer Institute | N=25 ➔ 0 | Terminated ➔ Withdrawn

Enrollment change • Trial withdrawal • Oncology • Ovarian Cancer • Solid Tumor

Autologous Dendritic Cell Vaccine in Kidney Cancer (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: Jodi Maranchie | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Intensive Locoregional Chemoimmunotherapy, Intradermal Autologous Alpha-DC1 Vaccines, and Systemic Pembrolizumab for Advanced-Stage Ovarian Cancer (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Kalinski, Pawel, MD, PhD

New P2 trial • Oncology • Ovarian Cancer • Solid Tumor

Type 1-polarized DC immunotherapeutic contains heterogeneous populations with IL-12p70 production restricted to a rare subset. (PubMed, bioRxiv) - "The distribution of αDC1 subclusters varied markedly between individuals and correlated with bulk cytokine and chemokine secretion profiles. Heterogeneity within αDC1 preparations may underlie inconsistent clinical trial outcomes, and identification of associated surface proteins provides a prospective strategy for subcluster enrichment to enhance DC release criteria and patient stratification for optimized therapeutic efficacy."

Heterogeneity • Journal • Oncology • IL12A • IL12B

Induction of HIV-Specific T Cell Responses Using αDC1 Pulsed With Conserved HIV-1 Peptides. (PubMed, J Immunol Res) - "After 48 h, αDC1 were harvested and cocultured with autologous T cells for 6 or 20 days. Pulsed-αDC1 were able to induce immune responses through the production of IFN-γ in T cells, with the subpopulation of effector memory CD4+ T cells (TEM) being responsible for the production of this cytokine after reexposure to the HIV antigens."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4 • CSF2 • IFNA1 • IFNG • IL1B • IL4 • TNFA

Assessment of silica nanoparticles internalization by alpha-type-1 polarized dendritic cells (αDC1) (AIDS 2026) - "The embargo on all abstracts, including oral abstract, poster exhibition, e-poster and late breakers, will lift on Monday, 27 July, 14:00 Brasilia Time (BRT). If an abstract is part of an official AIDS 2026 press conference that occurs before that time, the embargo on that abstract lifts at the start of the official press conference."

Human Immunodeficiency Virus • Infectious Disease

Activating anti-MDS immunity with polarized dendritic cell vaccines (AACR 2024) - "We hypothesized that restoration of this population using a novel DC vaccination approach - alpha-type-1 polarized dendritic cells (αDC1) - might compensate for this deficiency and restore immunity...To date, our results suggest that generation of MDS patient-derived αDC1 cells is feasible and additional work is being performed to fully characterize their ability to activate anti-MDS immune responses. Since αDC1s have an established safety profile in patients with solid tumors, we anticipate that we will be able to rapidly translate our results to the clinic."

IO biomarker • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor • CD40LG • CD80 • CD86 • CSF2 • IFNA1 • IFNG • IL1B • IL4 • TNFA

Generation of multi-epitope-specific T cells for adoptive cell therapy for solid tumors using polarized DCs (SITC 2025) - "Alpha-type-1 polarized dendritic cells (αDC1), a type of DCs induced by mediators of innate responses against viruses, are particularly effective in converting non-cytolytic CD8+ T cell into effector CTLs...All procedures were performed in compliance with relevant laws and institutional guidelines. Informed consent was obtained from all donors."

Oncology • Ovarian Cancer • Solid Tumor • CD8 • IFNG

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Roswell Park Cancer Institute | Trial completion date: Apr 2026 ➔ Jun 2025 | Active, not recruiting ➔ Terminated; Funding completed

Trial completion date • Trial termination • Melanoma • Oncology • Solid Tumor

Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines (clinicaltrials.gov) - P1/2 | N=25 | Terminated | Sponsor: Roswell Park Cancer Institute | Trial completion date: Jun 2026 ➔ Jun 2025 | Suspended ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Jun 2025; lack of funding

Trial completion date • Trial primary completion date • Trial termination • Oncology • Ovarian Cancer • Solid Tumor

Phase IIa study of αDC1 vaccines targeting HER2/HER3 combined with pembrolizumab in patients with asymptomatic brain metastasis from breast cancer. (ASCO 2025) - P2 | "So far, 7 of the planned 21 pts have been enrolled. Clinical trial information: NCT04348747."

Clinical • IO biomarker • P2a data • Brain Cancer • Breast Cancer • Glioma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CCR5 • CXCL10 • CXCL11 • CXCL9 • CXCR3 • ERBB3 • HER-2 • PD-L1

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=1 | Active, not recruiting | Sponsor: Roswell Park Cancer Institute | Recruiting ➔ Active, not recruiting | N=24 ➔ 1 | Trial completion date: Nov 2027 ➔ Apr 2026 | Trial primary completion date: Nov 2027 ➔ Apr 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Nov 2025 ➔ Nov 2027 | Trial primary completion date: Nov 2025 ➔ Nov 2027

IO biomarker • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • CD8

Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Roswell Park Cancer Institute | N=19 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

AIM ImmunoTech Highlights Key 2024 Achievements and Outlines Upcoming 2025-26 Value-Driving Milestones (GlobeNewswire) - "Phase 2 Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer: H1 2025: Expected last patient dosed and completion of study; Phase 2 Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines: H1 2025: First patient dosed."

Trial status • Ovarian Cancer • Solid Tumor

Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer (clinicaltrials.gov) - P2 | N=19 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Oct 2026 ➔ Feb 2027 | Trial primary completion date: Oct 2026 ➔ Feb 2027

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines (clinicaltrials.gov) - P1/2 | N=25 | Recruiting | Sponsor: Roswell Park Cancer Institute | Suspended ➔ Recruiting

Enrollment open • Metastases • Oncology • Ovarian Cancer • Solid Tumor • CCL2 • CCL22 • CCL3 • CD4 • CXCL10 • CXCL11 • CXCL12 • CXCL9 • FOXP3 • IFNG • IL10 • ITGAM • ITGAX

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Aug 2025 ➔ Nov 2025 | Trial primary completion date: Aug 2025 ➔ Nov 2025

Combination therapy • IO biomarker • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • CD8

Effects of Injectable Solutions on the Quality of Monocyte-Derived Dendritic Cells for Immunotherapy. (PubMed, J Immunol Res) - "Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70)...Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C."

Journal • Immunology • Infectious Disease • Oncology • CSF2 • IFNA1 • IFNG • IL1B • IL4 • TNFA

Autologous Dendritic Cell Vaccine in Kidney Cancer (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: Jodi Maranchie | Phase classification: P2a ➔ P2

Combination therapy • Phase classification • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ANXA5 • BTLA • CD31 • CD8 • ER • GZMB • IFNG • LAG3 • LAMP3 • NRP1 • PD-1 • PECAM1 • RGS5 • TIGIT

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Dec 2025 ➔ Aug 2025

Combination therapy • IO biomarker • Trial completion date • Melanoma • Oncology • Solid Tumor • CD8

Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer (clinicaltrials.gov) - P2 | N=19 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: May 2026 ➔ Oct 2026 | Trial primary completion date: May 2026 ➔ Oct 2026

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Rintatolimod, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Roswell Park Cancer Institute | Suspended ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor • CD8