Complete Response to PD-1 Inhibitor in Primary Hepatocellular Carcinoma Patients Post-Progression on Bi-Specific Antibody Conjugated CIK Cell Treatment: A Report of Two Cases

Abstract

Background Programmed death receptor-1 (PD-1) immune checkpoint inhibitors (ICIs) have produced encouraging results in hepatocellular carcinoma (HCC) patients. Cytokine-induced killer (CIK) cells treatment can specifically identify tumor-associated antigens and has encouraging preliminary efficacy for HCC. This study reported two cases of HCC patients achieved complete response (CR) by anti-PD-1 antibody therapy post-progression on bi-specific antibody conjugated CIK immunotherapy. Case Presentation Case one, a 75-year-old male, was diagnosed with the intrahepatic cholangiocarcinoma (ICC) in October 2017. After interventional, CIK, ablation and other comprehensive therapy, ICC was gradually cured. When new occurrence of HCC, he was treated with anti-PD-1 antibody therapy and achieved CR. Case two, a 65-year-old female, was diagnosed with HCC in July 2016. After progression on several ablation treatments, she received 8 cycles of CIK treatment and achieved stable disease (SD). After disease progressed on CIK treatment, she received 4 cycles of anti-PD-1 antibody therapy, finally achieved CR. Conclusion Anti-PD-1 antibody therapy after prior progression on bi-specific antibody conjugated CIK immunotherapy may be efficacy and safety for HCC patients.

Suppression of MUC1-Overexpressing Tumors by a Novel MUC1/CD3 Bispecific Antibody

“…Moreover, the immune checkpoint inhibitors (anti-PD1, anti-PDL1) have been successfully applied in clinical applications, and the combination of immune checkpoint inhibitors with the BsAb has been studied in many preclinical and clinical studies [ 51 ]. A recent study suggested that a MUC1/CD3 BsAb (PLGA nanoparticle connected with an anti-MUC1 mAb and anti-CD3 mAb) conjugated CIK cell therapy showed encouraging clinical results in hepatocellular carcinoma patients when combined with anti-PD1 treatment [ 42 ]. Therefore, in future work, the anti-tumor efficacy of MUC1/CD3 BsAb in combination with the immune checkpoint inhibitors may be worth studying.…”

“…are now under investigation [ 37 , 38 , 39 , 40 , 41 ]. Recently, a clinical study revealed that a MUC1/CD3 bispecific antibody conjugated CIK (cytokine-induced killer) cell therapy could lead to the complete response in primary hepatocellular carcinoma (HCC) patients when combined with PD1 inhibitor treatment [ 42 ]. This MUC1/CD3 bispecific antibody was generated via the connection of an anti-CD3 and anti-MUC1 mAb to a PLGA nanoparticle through a chemical reaction, and this BsAb could also elicit anti-tumor activity in lung cancer samples in another study [ 43 ].…”

Application of adoptive cell therapy in hepatocellular carcinoma

“…Synthetic small interfering (si)RNA targeting PD-1 transfected with CIK cells can target and kill tumour cells in liver cancer mice [137]. Recent studies have identified two cases after bispecific antibody-coupled CIK immunotherapy followed by complete remission with anti-PD-1 antibody therapy [138]. All of the above studies suggest that combination therapy with CIK may be an effective strategy for the targeted treatment of HCC.…”

Combination treatment of pembrolizumab with DC-CIK cell therapy for Advanced hepatocellular carcinoma: a case report

“…Checkpoint inhibitors and immune cell therapy have already been evaluated individually for their clinical efficacy on HCC. However, only one case report [ 4 ] discussed the effect of immune checkpoint inhibitors in combination with immune cell therapy to treat HCC.…”