Abstract
There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immuneactivating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8+ T-cell responses in this wellestablished solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection. Specifically, 48 hours after injection, 26.5%±16.9% of the injected PG-CpG dose versus 4.72%±2.61% of free CpG remained at the tumor, and 1.53%±1.22% of the injected PG-CpG versus 0.37%±0.33% of free CpG was retained in the draining inguinal lymph nodes. These findings indicate that PG is an effective synthetic polymeric carrier for delivery of immunostimulatory agents to tumors and lymph nodes.
Original language | English (US) |
---|---|
Pages (from-to) | 11-20 |
Number of pages | 10 |
Journal | Journal of Immunotherapy |
Volume | 40 |
Issue number | 1 |
DOIs | |
State | Published - 2017 |
Keywords
- B16-OVA melanoma
- CpG
- macrophage
- poly-L-glutamic acid
- tetramer-specific CD8 T cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology
- Cancer Research
MD Anderson CCSG core facilities
- Biostatistics Resource Group
- Flow Cytometry and Cellular Imaging Facility
- Research Animal Support Facility
- Small Animal Imaging Facility