Radio-Immuno-Modulation in Lung Cancer

Official Title

Radio-Immuno-Modulation for Advanced Lung Cancer: a Pilot Study Evaluating Tolerance and Immune Responses

Summary:

This project will assess the feasibility of treating advanced cancer using the immune system, without any anti-cancer drug. In this pilot study, the investigators propose combining low-dose radiation therapy, in lung cancer patients, with allogeneic immune cells obtained from a donor. The patients will receive radiation therapy directed to one of the patient's tumours, as well as an immunomodulatory drug called cyclophosphamide. Thereafter, they will receive the infusion of donor immune cells.

Trial Description

Primary Outcome:

  • Incidence of treatment-related adverse events
Secondary Outcome:
  • Immune responses - T cell infiltration
  • Immune responses - Tumour cell phenotype
  • Immune responses - tumour infiltrating T cell phenotype
  • Immune responses - origin of tumour infiltrating T cells
Metastatic lung cancer remains incurable despite numerous studies and treatments tried, including chemotherapy and, more recently, targeted therapies. Cancer can escape immune surveillance through different mechanisms: low levels of tumour associated antigens (TAA), regulatory T cells, and immunosuppressive cytokines. Non-cytolytic doses of radiation have been shown to reverse some of these pathways in experimental models. It up-regulated the density of the MHC molecules presenting TAA and increased the T cell infiltration of the tumour (1). Patients with lymphoma, liver or prostate cancer were treated with radiation therapy combined with immunotherapy, in the form of a TLR9 agonist, autologous dendritic cells or a prostate-specific antigen vaccine (2, 3, 4). These trials have shown an induction of T cell reactivity against TAA. Another form of immunotherapy, used for patients with refractory hematologic malignancies is allogeneic hematopoietic stem cell transplantation (HSCT) (5). Its success has relied on cell infusions from a donor, demonstrating the immunologic control sustained by allogeneic cells (6). The approach investigated in this study uses the immune cells from a donor to induce a tumour destruction reaction. This will be amplified by the immunological effects of radiation therapy. Many oncogenes are present in lung cancers and low-dose radiation increases their expression on the surface of the tumour cell. In addition, radiation has the property to stimulate the production of inflammatory cytokines and chemokines in the irradiated site. Finally, the donor's immune cells shall respond physiologically by migrating to the site of inflammation. This will trigger an immune reaction directed against the abnormal cancer cells. A total of 24 patients are expected to be recruited over the study period, estimated to be 3 years. The allogeneic cells will be obtained from one of two possible donor types. For patients having a living donor, the immune cells will be harvested through a collection procedure called apheresis. The living donor should be a sibling with 3/6 or less HLA compatibility with the patient, at the A, B and DRB1 loci. For patients who do not have such a living donor, allogeneic cells from a cryopreserved umbilical cord blood (UCB) unit will be used. The treatment course will be the following: low-dose radiation therapy will be delivered to a single tumour site, which could be either the primary tumour or one of its metastases. Low-dose cyclophosphamide will be given to decrease regulatory T cell activity and increase anti-tumour responses. Allogeneic immune cells will be administered thereafter, according to the treatment arm the patient has been assigned.

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society