Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 234-253 http://medscipublisher.com/index.php/cge 242 INTASYL™. The study showed that dual-target INTASYL™ had a synergistic antitumor effect in vivo, and immune regulatory mechanisms within the tumor microenvironment were assessed using flow cytometry. Additionally, the study confirmed the dose-dependent antitumor effects of the therapy and highlighted the potential for further development of this strategy to maximize efficacy and minimize immune-related side effects. 5.3 Combining immunotherapy with targeted therapy To improve the effectiveness of immunotherapy, researchers have combined immunotherapy with targeted therapeutic agents, including epidermal growth factor receptor (EGFR) inhibitors, VEGF/VEGFR inhibitors, human epidermal growth factor receptor 2 (HER2) inhibitors and multikinase inhibitors for colorectal cancer, and several studies have achieved better results, listed in Table 2. The AVETUX study combined anti-PD-L1, cetuximab, and chemotherapy demonstrated a 75% objective response rate and a 95% disease control rate(Tintelnot et al., 2022). Researches showed that increased CXCL10 expression had a sensitizing effect on the combination therapy with cetuximab and anti-PD-1 antibody in CRC (Yan et al., 2023). Targeted therapy not only stops the proliferation of tumor cells, but also establishes a favorable immune microenvironment for the effectiveness of immunotherapy(Singh et al., 2024). Therefore, the combination of targeted therapy and immunotherapy may produce greater efficacy than either treatment alone, as shown in Table 2. 5.4 Combining Immunotherapy with Chemotherapy Combining immunotherapy with chemotherapy can enhance anti-tumor immunity by inducing immunogenic cell death and modulating the tumor microenvironment. Chemotherapeutic agents can increase the release of tumor antigens, reduce immunosuppressive cells, and enhance the infiltration of effector T cells into the tumor. For example, the combination of doxorubicin with immune checkpoint inhibitors has shown significant improvements in tumor regression and immune response in preclinical models (Kuai et al., 2018; Taniura et al., 2020). Clinical trials combining immunotherapy with chemotherapy were shown in Table 3. Table 3 Combining Immunotherapy with Chemotherapy in colon cancer Trail name Sample size Treatment Phase Primary outcomes Results AtezoTRIBE (Antoniotti et al., 2022) 218 FOLFOXIRI + bevacizumab vs. FOLFOXIRI + bevacizumab + atezolizumab II PFS Atezolizumab group: 13·1 months (80% CI 12·5–13·8); Control group: 11·5 months (10·0–12·6) (HR: 0·69 [80% CI 0·56–0·85]; p=0·012; adjusted HR 0·70 [80% CI 0·57–0·87]; log-rank test p=0·018). NCT05171660 (Fang et al., 2023) 25 Sintilimab (IBI 308) + CAPEOX+ bevacizumab (BBCAPX) II ORR 84%; All patients with lung metastases had a response (n=4); The ORR in patients with liver metastases was 93.3% CheckMate 9X8 (Lenz et al., 2024) 195 Nivolumab+mFOLFO X6+bevacizumab (SOC) vs. SOC II ORR, DCR, PFS, OS NIVO+SOC group: ORR: 60%; median (95% CI) DOR: 12.9 (9.0-13.1) months; SOC group: ORR: 46%; median (95% CI) DOR: 9.3 (7.5-11.3) months. Abbreviations: Objective response rate (ORR), Disease control rate (DCR), Progression-Free-Survival (PFS), Overall survival (OS)
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