Cancer Immunology Reserch

CTG-initiated cryptic peptide translation up and downstream of a canonical ATG start codon is enhanced by TLR stimulation and induces tumor regression in mice

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Cancer Immunol Res. 2025 Jun 3. doi: 10.1158/2326-6066.CIR-24-0467. Online ahead of print. ABSTRACT Cytotoxic T-lymphocytes (CTLs) screen cells for signs of infection and transformation by recognizing peptides displayed on major histocompatibility complex (MHC) class I molecules. Next to canonical ATG-initiated open reading frames (ORFs), non-canonical translation can result in synthesis of non-conventional or `cryptic´ polypeptides. … Read more

Secretion of a VEGF-blocking scFv enhances CAR T-cell potency

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Cancer Immunol Res. 2025 Jun 2. doi: 10.1158/2326-6066.CIR-24-0876. Online ahead of print. ABSTRACT CAR T-cell therapy is an effective treatment strategy in B-cell malignancies, however, its efficacy in solid tumors remains limited. VEGF-targeted drugs are used as antitumor agents to target abnormal tumor vasculature, however, toxicities associated with systemic VEGF blockade limit their maximal therapeutic … Read more

Single-cell analysis of post-translational modifications identifies immunosuppressive macrophage subtypes in the HBV-positive hepatocellular carcinoma microenvironment

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Cancer Immunol Res. 2025 Jun 2. doi: 10.1158/2326-6066.CIR-24-1298. Online ahead of print. ABSTRACT Analysis of post-translational modifications (PTMs) of proteins can provide new insight, beyond that obtained from analysis of protein levels, for understanding the tumor microenvironment (TME). The characteristics of PTMs in immune cells, along with their spatial distribution, have not been comprehensively integrated, … Read more

The effects of clinically relevant radionuclides on the activation of a type I interferon response correlate with radionuclide half-life and linear energy transfer and influence radiopharmaceutical antitumor efficacy

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Cancer Immunol Res. 2025 May 29. doi: 10.1158/2326-6066.CIR-24-1191. Online ahead of print. ABSTRACT Radiopharmaceutical therapies (RPT) activate a type I interferon (IFN1) response in tumor cells. We hypothesized that the timing and amplitude of this response varies by isotope. We compared equal doses delivered by 90Y, 177Lu, and 225Ac in vitro as unbound radionuclides and … Read more

Nanobody-Directed CEA-targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts

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Cancer Immunol Res. 2025 May 29. doi: 10.1158/2326-6066.CIR-24-0137. Online ahead of print. ABSTRACT Gastrointestinal cancers (GICs), including gastric cancers (GCs) and colorectal cancers (CRCs), are among the leading causes of cancer-related deaths worldwide. Metastatic GCs and CRCs often develop resistance or fail to respond to current therapies. Adoptive T-cell immunotherapy, especially with T cells expressing … Read more

PIKfyve inhibition induces antitumor immunogenicity by attenuating STING trafficking and lysosomal degradation

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Cancer Immunol Res. 2025 May 22. doi: 10.1158/2326-6066.CIR-24-0405. Online ahead of print. ABSTRACT Significant progress in the application of immune checkpoint blockade (ICB) for the treatment of multiple types of cancers has been achieved, but its overall response rate and therapeutic efficacy remain unsatisfactory. To address these limitations, the identification of a combinational approach to … Read more

IGM-7354, an immunocytokine with IL-15 fused to an anti-PD-L1 IgM, induces NK and CD8+ T cell-mediated cytotoxicity of PD-L1 positive tumor cells

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Cancer Immunol Res. 2025 May 22. doi: 10.1158/2326-6066.CIR-24-0937. Online ahead of print. ABSTRACT IgM antibodies are preformed pentameric or hexameric molecules that can be engineered to generate high affinity and high avidity fully human antibody therapeutics. In this study, we report an immunocytokine, IGM-7354, which was designed to bind multiple PD-L1 receptors while trans-presenting a … Read more

TCR-based therapy directed against kallikrein-related peptidase 4 is safe and effective against prostate cancer

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Cancer Immunol Res. 2025 May 19. doi: 10.1158/2326-6066.CIR-24-0119. Online ahead of print. ABSTRACT The efficacy of most immunotherapies for prostate cancer is limited by poor tumor immunogenicity, evidenced by minimal T-cell infiltration. Treatment with T cells engineered to express T-cell receptors (TCR) targeting prostate-specific antigens offers a potential solution by bypassing endogenous T-cell repertoire limitations. … Read more

Combination Therapy Approaches to Enhance the Efficacy of ERV-Targeting Vaccines in Cancer

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Cancer Immunol Res. 2025 May 19:OF1-OF12. doi: 10.1158/2326-6066.CIR-24-1192. Online ahead of print. ABSTRACT Endogenous retroviruses (ERV) are the genetic remnants of retroviruses in which proviral sequences integrated into germline cells of our ancestors. Although the vast majority of ERV sequences have accumulated mutations over the course of human evolution, some still contain open reading frames … Read more

Identification of the distinct immune microenvironment features associated with progression following high dose melphalan and autologous stem cell transplant in multiple myeloma

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Cancer Immunol Res. 2025 May 8. doi: 10.1158/2326-6066.CIR-25-0019. Online ahead of print. ABSTRACT A key treatment for patients with multiple myeloma is high-dose melphalan followed by autologous stem cell transplant (ASCT). It can provide a deep response with long-term remission. However, some patients progress quickly, and it is not clear why that is. Here, we … Read more

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