Interferons are naturally occurring lymphokines that are normally produced in response to viral infection. Their mechanism of action in malignant disease is uncertain;
they have specific antiproliferative activity but can also induce natural killer cells and other immunological changes that might have an antitumour effect.
lFN-a is now commercially available and is being used in several haematological malignancies, e.g. hairy cell leukaernia and chronic myeloid leukaemia. In the latter, it results in a reduction in the proportion of Philadelphia (Ph) chromosome positive cells in at least 50% of patients, with total elimination in 10%. It remains to be established whether these effects will translate into prolongation of survival. lFNs are also being tested in an ‘adjuvant’ setting in follicular lymphoma and myeloma. The treatment has side-effects, mainly flu-like symptoms which tend to diminish with time. The main disadvantage is that lFN has to be given as a subcutaneous injection. Colony stimulating factors (growth factors).
Granulocyte and granulocyte/macrophage colony stimulating factors (G-CSF and GM-CSF) are being evaluated in patients with cancer:
• To reduce the duration of neutropenia following chemotherapy
• In conjunction with chemotherapy, to stimulate the proliferation of haemopoietic progenitor cells in the marrow so that they enter the circulation and can be collected from the peripheral blood to support very intensive therapy
• In acute myelogenous leukaemia, to induce leukaemic blast cells into cycle in the hope of increasing cell kill by cell-cycle specific drugs such as cytosine arabinoside Monoclonal antibodies Monoclonal antibodies directed against tumour cell surface antigens are being investigated in three experimental settings:
1 In vitro, in conjunction with complement, to deplete autologous bone marrow of tumour cells in patients with leukaemia and lymphoma receiving very intensive therapy with autologous bone marrow transplantation.
2 In vitro, in conjunction with complement to deplete allogeneic bone marrow of mature T cells which cause graft-versus-host disease
3 In vitro, conjugated to a toxin, e.g. ricin, or in vivo to a radioactive element, e.g. iodine/yttrium, to deliver the cell killing substance directly to the tumour cell.