Norwood Immunology gets IND for bone marrow therapy

Melbourne immune therapy developer Norwood Immunology Ltd (AIM:NIM) has announced that the US Food and Drug Administration has granted investigational new drug (IND) approval for its first bone-marrow transplant trial in cancer patients

Norwood and its US partner, TAP Pharmaceutical, applied to the FDA in December to run the trial, which will test whether TAP's drug Lupron, which rejuvenates the thymus gland, boosts the recovery of cancer patients' immune responses in the wake of high-dose radiotherapy or chemotherapy.

The thymus gland, high in the chest, is where cancer-fighting cytoxic T-cells are 'taught' to identify and destroy virus-infected or cancerous cells. Normally, the thymus shrinks in late teenage, and the flow of new T-cells slows to a trickle, impairing the immune system's capacity to detect cancerous cells and fight off viral infections.

In the 1990s, Monash University researcher Professor Richard Boyd found that TAP's Lupron, by suppressing the production of sex-hormones that cause the thymus to atrophy, caused the organ to regrow and resume production of new T-cells.

The Norwood-TAP Phase II study is a pilot trial, aimed at determining if drug therapy to rejuvenate the thymus produces a more rapid and complete recovery of the immune response in severely immuno-compromised patients after an autologous bone-marrow transplant, where the patient's bone marrow is extracted beforehand, and returned to the patient after aggressive cancer therapy.

The trial will be conducted at the M.D. Anderson Cancer Centre in Houston, Texas, and will involve a consortium of eminent clinicians from of America's leading cancer centres, led by Dr Lee Nadler, of the Dana-Farber Cancer Institute at Harvard medical School.

The trial, which is expected to enroll its first patients within three months, is being co-funded by the National Cancer Institute and the National Institute of Allergy and Infectious Diseases.

Researchers will evaluate the therapy by measuring the patients' immune responses to four vaccines, as an indication of improved immune function after their "self" bone marrow transplants.

Norwood's chief operating officer, Dr Suzanne Lipe, said that if the therapy works, stem cells in the engrafted bone-marrow will migrate to the thymus and undergo maturation. The 'programmed' T-cells will then re-enter the circulation to fight off infection and mop up residual cancerous cells that have evaded chemotherapy or radiotherapy.

Lipe said if the date from the pilot trial shows the therapy safely induces 'rebooting' of the immune response, Norwood plans to run a similar trial with an allogenic (donor) bone-marrow transplant.

She said theory and experiment suggest that the donor stem cells will mingle with the patient's own stem cells during thymic maturation, giving rise to a chimeric population of T-cells that, in addition to being primed to fight infection and cancer, will also 'learn' to recognise transplanted organs as "self".

If the therapy induces tolerance of donor organs, it would avoid the need to treat transplant recipients with powerful immunosuppressant drugs that expose them to an increased risk of cancer and infection.