β -Alethine, An Immunostimulatory Drug That Synergizes With Anti-PD1 Therapy
Guth, A.1 andTaub, F.2*
1Colorado State University 2FindCure.org
In humans, β-alethine has previously been found to be non-toxic, with no drug related adverse reactions reported in Phase I/II, modulate the immune system and reduce even large lymphoma masses (up to 75% decrease in volume) in patients who have been heavily pretreated so long as they are not anergic. As a single agent, it was shown to reduce the growth of slow-growing myeloma and melanoma in mouse tumor models. For more aggressive or faster growing murine tumors, including breast cancer and B16 melanoma, combination therapy of β-alethine with chemotherapeutics was more effective than the chemotherapeutic alone, resulting in reduction of both primary tumor and in the development of metastases. Of note, β-alethine did not increase toxicity due to the chemotherapy, in fact, it appeared to decrease toxicity.
Recently we have found that application of β-alethine to mouse cells in vitro or injection into intact mice modulates the number of cells expressing checkpoint inhibitors and the level of checkpoint inhibitors on their surface. In order to evaluate anti-cancer activity, DBA mice were given the syngeneic Cloudman melanoma. Tumors were allowed to
grow for 15 days. Mice were treated either vehicle, β-alethine (s.c.) and/or anti-PD1 (50 ug/mouse, i.p.). Anti-PD1 and β-alethine, as single agent therapies, appeared to potentially slow the growth of the melanoma, but this effect was not statistically significant for individual groups. However, the combination of anti-PD1 and β-alethine completely stopped melanoma growth and this effect was highly statistically significant (p < .000). Thus, therapeutic application of β-alethine in combination with checkpoint therapies may enhance the checkpoint therapies, potentially allowing for greater effectiveness and/or a lower dose of these therapeutic antibodies.
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