Using smart biomaterials with immunoadjuvants to treat metastatic breast cancer
Mentor: Wilfred Ngwa, PhD (Dana Farber Cancer Institute)
In the field of oncology, the abscopal effect refers to the phenomenon when localized therapy at one site can cause tumor regression at distant untreated sites. But the occurrence of this effect is rarely observed naturally without the presence of aid. Recent research in oncology confirms that the combination of radiation and the use of smart biomaterials with immunoadjuvants can be used to prime the abscopal effect. Talazoparid (TLZ) is a PARP inhibitor that has shown an ability to promote antitumor activity in breast cancer patients with both inherited BRCA1/2 mutations and non-inherited inactivation of BRCA1/2 genes. TLZ is only available in an oral form and therefore must be taken in high quantities which results in side effects including bone marrow toxicity, nausea, and fatigue. An implant delivery depot named InCeT-TLZ has been developed with nanoparticles, which can be injected directly in the tumor where it will act as a sustained release depot of TLZ over a prolonged period. The central hypothesis for this project is that releasing TLZ through InCeT-TLZ in combination with an immunoadjuvant will boost the abscopal effect, with minimal toxicities to nontarget organs. The project involves both in-vivo and in-vitro studies to test the hypothesis.
This figure displays a detailed account of the abscopal effect. First, the radiation causes the targeted tumor to release neoantigens. Those antigens are then taken up by antigen-presenting cells (APCs) and taken to the lymph node to prime naive CD8+ T cells. Once the CD8+ T cells are activated, they can be directed to infiltrate both the irradiated tumor and the nonirradiated tumor. Immunoadjuvants are loaded in SRBs and/or nanoparticles so that they can be released to increase abscopal responses. Source: Ngwa W, et al. Using immunotherapy to boost the abscopal effect. Source: