Antisense102: Pilot Immunotherapy for Newly Diagnosed Malignant Glioma
Status:
Completed
Trial end date:
2020-08-17
Target enrollment:
Participant gender:
Summary
This human Phase 1 trial is a continuation of a Phase 1 trial which enrolled patients with
recurrent gliomas (#TJU-14379-101) and which was designed after a previously conducted Phase
1 human trial at our institution. With certain modifications, it is intended to reproduce the
safety results of the recurrent glioma previous trials as well as explore any objective
clinical responses in newly diagnosed patients. Protocol 14379-101 is closed to accrual and
Abbreviated Clinical Report is prepared for FDA submission. The safety profile for this
protocol was quite favorable.
This treatment involves taking the patient's own tumor cells at surgery, treating them with
an investigational new drug (an antisense molecule) designed to shut down a targeted surface
receptor protein, and re-implanting the cells, now encapsulated in small diffusion chambers
the size of a nickel in the patient's abdomen within 24 hours after the surgery. Loss of the
surface receptor causes the tumor cells to die in a process called apoptosis. As the tumor
cells die, they release small particles called exosomes, each full of tumor antigens. The
investigators believe that these exosomes as well as the presence of the antisense molecule
work together to activate the immune system against the tumor as they slowly diffuse out of
the chamber. Immune cells are immediately available for activation outside of the chamber
because a wound was created to implant these tumor cells and a foreign body (the chamber) is
present in the wound. In this trial, a dose escalation of the therapeutic agent will involve
an increase in both biodiffusion chamber number as well as the time the biodiffusion chambers
remain implanted. The wound and the chamber fortify the initial immune response which
eventually leads to the activation of immune system T cells that attack and eliminate the
tumor. By training the immune system to recognize the tumor, the patient is also protected
through immune surveillance from later tumor growth should the tumor recur. Compared to
treatment alternatives for tumor recurrence, including a boost of further radiation and more
chemotherapy, this treatment represents potentially greater benefit with fewer risks.