Cancer

MIS416 for Cancer Therapy

The activation of the body's innate anti-tumor immune mechanisms by immunostimulatory compounds is now a well established therapeutic approach for the treatment of cancer. A key cellular target for immune modulation are natural killer (NK) cells which play a central role in tumor cell immunosurveillance and destruction. In addition NKT, myeloid and plasamacytoid dendritic cells as well as monocyte/macrophages represent additional arms of innate anti-tumor immunity which kill tumor targets by several non-redundant mechanisms including granzyme, perforin, Fas-FasL, and TNF-alpha. Since these subsets also underpin adaptive immune responses, appropriate immune modulation in concert with tumoricidal activity and the presentation of antilogous tumor antigen may lead to autoimmunization.

MIS416 has anti-metastatic activity as a stand-alone agent or co-therapy

Broadly active immune cell-specific immunostimulants that can be administered systemically may be more able to control metastatic disease arising spontaneously or as a result of cell dissemination following tumor surgery than existing cytotoxic drugs or single agent IRM. In pre-clinical Lewis lung and 4T1 mammary tumor metastatic models, MIS416 therapy alone has been shown to significantly reduce the occurrence of lung metastases when administered as a single i.v bolus at various time points following establishment of a tumor burden. Further, when used as a co-therapy with local tumor irradiation, there is a further reduction in the number of lung metastases in the Lewis lung model compared to individual therapies alone. In this model, the weight loss associated with radiation toxicity is also ameliorated with MIS416 co-therapy, providing evidence of additional radioprotective effects being elicited by MIS416 therapy.

MIS416 therapy induces tumor-specific immunity

There is a great need for the development of therapeutic cancer vaccines which enhance the ability of the patient's immune system to immunologically control the disease, leading to a reduction in severity or complete elimination. To date developments have fallen short of expectations in part due to the failure of patients to respond adequately to the vaccine adjuvant component. The potential use for MIS416 as a therapeutic cancer vaccine adjuvant has been recently demonstrated in a B16-OVA tumor vaccine model. Treatment with MIS416 following tumor inoculation in the absence of exogenous tumor antigen not only inhibited tumor growth, but also induced a significant increase in the number of OVA-specific IFN-gamma secreting CD8+ cells. These findings are important from a therapeutic standpoint, since they underscore the paradigm that appropriate immunostimulation in concert with endogenous tumor antigen can lead to autoimmunization.

Publications:

Novel microparticle immune response modifier shows broad spectrum effects against recurrent cancer or metastatic disease
- Preclinical data presented at 2009 AACR Annual Meeting.

Informational Links:

Combining Innate Immunity with Radiation Therapy for Cancer Treatment
- from Clinical Cancer Research, 2005