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Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity are known and used, they often fail to achieve satisfactory long-term patient outcomes and survival. Recently, immunotherapy has shown success in patients by harnessing important interactions between the immune system and cancer. However, many of these therapies lead to frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, in severe cases, fatalities. New therapeutic approaches like intratumoral immunotherapy, characterized by reduced side effects, cost, and systemic toxicity, offer promising prospects for future applications in clinical oncology. In the context of locally advanced or metastatic cancer, combining diverse immunotherapeutic and other treatment strategies targeting multiple cancer hallmarks appears crucial. Such combination therapies hold promise for improving patient outcomes and survival and for promoting a sustained systemic response. This review aims to provide a current overview of immunotherapeutic approaches, specifically focusing on the intratumoral administration of drugs in patients with locally advanced and metastatic cancers. It also explores the integration of intratumoral administration with other modalities to maximize therapeutic response. Additionally, the review summarizes recent advances in intratumoral immunotherapy and discusses novel therapeutic approaches, outlining future directions in the field.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754201 | PMC |
http://dx.doi.org/10.3389/fimmu.2024.1479483 | DOI Listing |
Cancer Immunol Res
September 2025
Alligator Bioscience (Sweden), Lund, Sweden.
Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. Here, we describe ATOR-4066, a bispecific antibody that targets CD40 and CEACAM5 developed for immunotherapy of cancer using the Neo-X-Prime platform.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Pathological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and tumor heterogeneity, continue to limit the therapeutic advantages of OVT as a standalone modality and hindered its clinical success.
View Article and Find Full Text PDFFASEB J
September 2025
Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Tumor-associated macrophages (TAMs) act as a vital player in the immunosuppressive tumor microenvironment (TME) and have received widespread attention in the treatment of cancer in recent times. Nevertheless, simultaneously inducing TAM repolarization and strengthening their phagocytic ability on cancer cells is still a significant challenge. Ferroptosis has received widespread attention due to its lethal effects on tumor cells, but its role in TAMs and its impact on tumor progression have not yet been defined.
View Article and Find Full Text PDFAutophagy
September 2025
Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Immune checkpoint inhibitors (ICIs) can re-active the immune response and induce a complete response in mismatch repair-deficient and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, most CRCs exhibit proficient mismatch repair and microsatellite stable (pMMR/MSS) phenotypes with limited immunotherapy response because of sparse intratumoral CD8 T-lymphocyte infiltration. Cellular senescence has been reported to involve immune cell infiltration through a senescence-associated secretory phenotype (SASP).
View Article and Find Full Text PDFJ Control Release
September 2025
School of Pharmaceutical Sciences, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:
Fusobacterium nucleatum (Fn.) can colonize breast cancer tissue to promote tumor progression by inducing immunosuppression. Targeted therapeutic strategies against intratumoral bacteria remain unexplored and have potential in tumor immunotherapy.
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