CDX-1401

CDX-1401 is a cancer vaccine developed by Celldex Therapeutics. It consists of a fusion protein that combines a fully human monoclonal IgG1 antibody targeting the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen[1][6][8]. This design allows the vaccine to specifically target dendritic cells in vivo, which has been a significant challenge in developing protein-based vaccines[6]. ## Mechanism of Action CDX-1401 works by targeting dendritic cells through the DEC-205 receptor. When the vaccine binds to this receptor, it delivers the NY-ESO-1 tumor antigen to dendritic cells, which then process and present it to T cells. This stimulates the immune system to recognize and attack cancer cells that express the NY-ESO-1 protein[6][8]. The NY-ESO-1 protein is primarily expressed in cancer cells and only in a few types of normal cells, making it an ideal target for cancer immunotherapy[4]. By targeting this protein, CDX-1401 aims to generate both antibody and T-cell responses against tumors that express NY-ESO-1[6]. ## Clinical Development CDX-1401 has been studied in several clinical trials: 1. **Phase I/II Trial**: An open-label, dose-escalation study in patients with malignancies known to express NY-ESO-1. In this trial, CDX-1401 was administered with immune stimulants Resiquimod and/or poly-ICLC (Hiltonol) to enhance the immune response[4]. 2. **Phase I Results**: The Phase I study demonstrated that CDX-1401 could safely lead to robust humoral and cellular immunity. It was the first clinical study to show that an off-the-shelf vaccine targeting dendritic cells in vivo through DEC-205 could achieve this outcome[6]. Final data from this study were published in Science Translational Medicine[6]. 3. **Phase II Trial**: A randomized study comparing two treatment approaches: - Cohort 1: CDX-1401 with poly-ICLC plus pretreatment with CDX-301 (a recombinant human Flt3 ligand) - Cohort 2: CDX-1401 with poly-ICLC without CDX-301[1][5][8] The Phase II results showed that adding CDX-301 nearly doubled the vaccine's efficacy. Patients who received the combination showed immune responses significantly earlier and at much higher levels compared to those who received only the vaccine[8]. The treatment was well-tolerated with mostly grade 1-2 adverse events including chills, injection site reactions, fever, and myalgias[1]. ## Target Population CDX-1401 has been primarily studied in: 1. Patients with resected melanoma (Stage IIB-IV)[1][5] 2. Patients with malignancies known to express NY-ESO-1[4] The vaccine appears particularly promising for the adjuvant setting in melanoma, where patients have a 20-60% recurrence rate with 5-year overall survival between 45% and 70%[1]. ## Combination Approaches CDX-1401 has shown enhanced efficacy when combined with: 1. **CDX-301 (Flt3L)**: This recombinant human Flt3 ligand expands the number of circulating dendritic cells, enhancing the immune response to the vaccine[1][8]. 2. **Poly-ICLC**: This immune stimulant helps dendritic cells mature so they can better recognize tumors[5]. 3. **Checkpoint inhibitors**: Preliminary findings suggest potential benefits when CDX-1401 is followed by therapy with checkpoint inhibitors, providing rationale for combination immunotherapy strategies[6]. The combination of CDX-1401, CDX-301, and poly-ICLC has demonstrated the ability to generate integrated immunity (both humoral and cellular), yield higher levels of T-cell immunity, and provide durable responses over several months[8].

Other names

rasdegafusp alfaDEC-205/NY-ESO-1 fusion protein vaccine