NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

Merck is combining Keytruda with an autologous dendritic cell vaccine delivered intratumorally in a trial to treat non-hodgkin lymphoma (NHL). So dendritic cell vaccines can also be used to treat hematological cancers. (NHL is considered a blood cancer because it begins in the lymphatic system, where white blood cells [lymphocytes] grow abnormally and can form tumors throughout the body).

The phase I trial showed impressive safety and efficacy results:

We have completed a Phase I study treating NHL patients with cryoablation and intra-tumor injections of autologous DC into the cryoablated tumors. This treatment was very well tolerated with no major adverse events. More importantly, abscopal systemic response was seen with this non-toxic, localized immunotherapy approach. Five of the 10 treated patients had partial response with an average time to progression of 64 weeks (range 51-80 weeks). Building on this promising approach, we have identified two deficiencies that can be targeted with PD-1 blockade: 1. DCs have increased PD-L1 (programmed death ligand-1) expressions that impairs their ability to prime CD8 T cell for antigen-specific responses; 2. Increased presence of a novel population of tumor-reactive CD8 T cells in the blood and tumors of lymphoma patients with decreased effector functions and capacity to differentiate into memory cells. We hypothesize that the combination of PD-1 blockade with monoclonal antibody Pembrolizumab (supplied by Merck), cryoablation and intra-tumor DC therapy will improve clinical efficacy through improved anti-lymphoma immunity through a combination of increased antigenic response, increased effector function and or decreased immunosuppressive phenotype.

PD-1 blockade with cryoablation and dendritic vaccine to treat lymphoma
https://grantome.com/grant/NIH/R01-CA219960-01

Recruiting for the single-arm phase II trial was paused last time I checked in April, but it’s now recruiting again:

Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma
https://clinicaltrials.gov/ct2/show/NCT03035331


I emailed the Mayo Clinic and asked for information about the dendritic cell vaccine but they only replied that it’s not sponsored by any company. I believe the same vaccine is being used in another combination with Keytruda to treat late-stage inoperable Melanoma:

Dendritic Cell Therapy After Cryosurgery in Combination With Pembrolizumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Remove by Surgery
https://clinicaltrials.gov/ct2/show/NCT03325101


Anyway, this was interesting to me on many levels . . .