Résumé
Objective:To evaluate the efficacy and safety of disitamab vedotin combined with tislelizumab in the neoadjuvant treatment of bladder cancer.Methods:The clinical data of 16 bladder cancer patients who received neoadjuvant therapy with disitamab vedotin combined with tislelizumab from April 2022 to January 2023 at the First Hospital of Chongqing Medical University were retrospectively analyzed. There were 15 males and 1 female, aged (66.12±14.37) years old. The immunohistochemical staining of biopsy pathology showed that HER-2 (0), (+ ), (+ + ), and (+ + + ) were in 1, 6, 6, and 3 cases, respectively. Before neoadjuvant therapy, 5 cases were in T 2N 0M 0 stage, and 11 cases were in T 3N 0M 0 stage. Biopsy pathology showed 3 cases were low-grade uroepithelial carcinoma, and 13 cases were high-grade uroepithelial carcinoma. Neoadjuvant therapy regimens: Disitamab vedotin 120 mg, every 2 weeks for 1 cycle, a total of 4 cycles. Tislelizumab 200 mg, every 3 weeks for 1 cycle, a total of 3 cycles. Surgery was performed at 2-3 weeks after neoadjuvant therapy. The efficacy and adverse effects of neoadjuvant therapy were analyzed. Results:All 16 cases completed neoadjuvant therapy.Five cases achieved complete remission, 7 cases achieved partial remission, 3 cases had stable disease, and 1 case had disease progression.Twelve cases(75.0%) achieved objective remission, 15 cases (93.8%) had disease control, and 14 cases(87.5%) had a reduction in the target lesion from baseline. Complete remission was achieved in 2 (22.2%)of 9 HER-2-positive patients and and 3 (42.9%) of 7 HER-2-negative patients, respectively, and objective remission was achieved in 8 (88.9%) and 4 (57.1%). After neoadjuvant treatments, surgical treatments were refused in 6 cases, and bladder-preserving combination therapy was performed in 2 cases. Radical cystectomy were performed in 8 cases, with negative margins for surgical incision, of which 5 cases (62.5%) had postoperative pathologic stage <T 2, and 2 cases (25.0%) reached pathological complete remission. Only 2 cases developed postoperative related complications, all of which improved with treatment. Grade 3-4 adverse reactions of neoadjuvant therapy included elevated blood glucose in 2 cases (12.5%), elevated ALT in 1 case (6.3%), hypertriglyceridemia in 1 case (6.3%), and leukopenia in 1 case (6.3%). Immune-related adverse reactions included rash in 3 cases (18.8%), hypothyroidism in 2 cases (12.5%), and immune colitis in 1 case (6.3%). Conclusions:In the neoadjuvant treatment of bladder cancer, disitamab vedotin combined with tislelizumab has high objective remission rate and disease control rate, low incidence of serious adverse reactions and high rate of negative surgical margins. It also has better efficacy in HER-2 negative patients.
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Objective To evaluate the efficacy and safety of tislelizumab combined with chemotherapy in the treatment of urothelial carcinoma in the real word. Methods We enrolled 32 patients with urothelial carcinoma who were treated with tislelizumab and chemotherapy (gemcitabine/cisplatin or paclitaxel). The incidence of treatment-related adverse reactions during treatment and the efficacy evaluation were statistically analyzed. Results All patients were divided into two groups: 15 patients in the tislelizumab combined with paclitaxel group and 17 patients in the tislelizumab combined with GC group. Among 24 efficacy-evaluable patients, the ORR was 54.2% and the DCR was 83.3%. The ORR were 50.0% and 58.3%, and the DCR were 75.0% and 91.7% in the tislelizumab combined with paclitaxel group and the tislelizumab combined with GC group respectively. Common treatment-related adverse reactions included anemia (56.3%), loss of appetite (53.1%) and skin pruritus (50.0%). The grade 3-4 treatment-related adverse events occurred in 21.8% of patients. Common immune-related adverse reactions included skin toxicity (53.1%) and immune colitis (9.4%). Conclusion Tislelizumab combined with chemotherapy on urothelial cancer has significant curative effect, safety and controllability, but attention should be paid to immune-related adverse reactions.
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Objective To investigate the influence of m4-1BBL on the anti-tumor effects induced by truncated human prostate specific membrane antigen (tPSMA) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL (pDC316-tPSMA-IRES-m4-1BBL), pDC316-tPSMA and pDC316 were constructed. C57BL/6 mice were vaccinated in the quadriceps femoris, respectively. The CTL activity of spleen cells from the immunized mice against prostate cancer RM-1-tPSMA was detected by CCK-8 kit in vitro. The tumor growth was then observed. Results The target cell specific cytotoxicity rate induced by pDC316-tPSMA-IRES-m4-1BBL was 42.6%, compared to 24.8% in the pDC316-tPSMA group and 10.8% in the pDC316 group. The difference was significant (P<0.05). The volume of tumor in the pDC316 group was 2657.4mm3 7 d after vaccination, compared to 1334.5 mm3 in the pDC316-tPSMA group, 9 d after vaccination. In the pDC316-tPSMA-IRES-m4-1BBL group, the tumor volume was 445.8 mm3, 12d after vaccination. The difference was significant (P<0.05). Conclusion Gene vaccines co-expressing tPSMA gene and m4-1BBL gene could significantly enhance anti-prostate cancer effects in mice.