Cancer immunotherapy utilizing immune checkpoint inhibitors has been heralded as one of the most important scientific and medical breakthroughs in the early 21st century. It has revolutionized the standard of care in many challenging cancer types including colon cancer, melanoma, and Hodgkin lymphoma, leading to unprecedented clinical responses in these challenging tumors. Despite this, most patients fail to adequately respond to these treatments due to the lack of appropriate T cells within the tumor microenvironment. Further strategies are needed to enhance the T cell infiltrate and boost endogenous antitumor immunity. Many promising strategies have been developed; however, they are often associated with immune-related adverse events and require expensive patient-specific formulations. In this work, we aim to develop an in-situ cancer vaccine that relies on endogenous patient-specific tumor neoantigens. The benefit of this approach is that it can be tumor agnostic and is readily available without additional formulation. To achieve this, we engineered CpG-p(PDS-Man), a potent adjuvant-polymer conjugate able to bind unpaired cysteines on the tumor cell surface and on extracellular tumor debris in the tumor microenvironment. CpG is a potent adjuvant in clinical development and conjugating it to our cysteine binding polymer allows for sustained delivery in the tumor microenvironment, eliciting a strong antitumor immune response against endogenous tumor antigens. In this work, we found that our CpG-p(PDS-Man) conjugate could be readily constructed and purified. Upon intratumoral injection, CpG-p(PDS-Man) prolonged survival in multiple murine tumor models, including in tumors resistant to checkpoint inhibitors, such as the B16F10 melanoma. Furthermore, we found decreased systemic toxicity of our construct compared to free adjuvant. Our developed platform demonstrates a flexible, ready-to-use adjuvant-based immunotherapy that can trigger a widespread anti-tumor immune response with the appropriate vigor for successful treatment. Our research illustrates the potential of using CpG-p(PDS-Man) as a treatment platform for various types of cancer.