PMC8702989_01
Three times of liver biopsy and the main immunohistochemical indexes. (A) On November 01, 2017, the patient presented with intrahepatic cholangiocarcinoma with low differentiation; the immunohistochemical results showed muc-1 (+), GPC-3 (-), Hepa (-), CK7 (+), CK19 (+), AFP (-), Ki67 (70%+). (B) Postoperative pathology showed the combined HCC and ICC (cHCC-ICC), moderately differentiated; the immunohistochemical results showed muc-1 (scattered+), GPC-3 (oven +), CK7 (+), CK19 (+), AFP (-), Ki67 (30%+). (C) Postoperative pathology showed HCC, moderately differentiated; the immunohistochemical results showed GPC-3 (part weak+), muc-1 (-), CK7 (part +), CK19 (-), CD34 + (blood vessels+), CD10 (+), Ki67 (< 5% +), AFP (-).
OTT-14-5447-g0001.jpg
PMC8702989_01_OTT-14-5447-g0001.jpg
f0001
The pathological results of liver biopsy showed intrahepatic cholangiocarcinoma (ICC), poorly differentiated, MUC-1 positive (+) (Figure 1A). In March 2018, the abdominal CT showed he had increased residual activity of lesion in liver S6 and new active lesions in liver S5, and little change of remaining lesions, and the efficacy was assessed as progressive disease (PD, Supplementary Figure 1). ICC (cHCC-ICC), moderately differentiated (Figure 1B). Immunohistochemical results showed that GPC-3 (+), tumor mutation load (TML) was 20.1 Muts/Mb (TMB-H) with no other significant mutations. On December 19, 2019, the patient was performed with liver biopsy again, postoperative pathology showed HCC, moderately differentiated (Figure 1C).
Changes of (A) right lobe lesions and (C) tumor markers during bi-specific antibody conjugated CIK treatment from February to December 2019. (B) The efficacy was assessed as CR after the patient injected with PD-1 and (D) Biomarker curve from April to October 2020.
OTT-14-5447-g0002.jpg
PMC8702989_02_OTT-14-5447-g0002.jpg
f0002
From October 2018 to March 2020, she was enrolled in the clinical trial "A Randomized, Controlled Phase II Clinical Study of Activated CIK Armed with Bispecific Antibody for Advanced Liver Cancer" (NTC03146637), and were treated with bi-specific antibody conjugated CIK Cells (GPC-3) for 4+4 cycles (Supplementary Figure 2).
(A) The pathological results showed that moderately differentiated of HCC. (B) Changes of AFP and (C) imaging before and after bi-specific antibody conjugated CIK treatment from October 2018 to March 2020. Red arrows pointed to target lesions and red circles marked non-target lesions.
OTT-14-5447-g0003.jpg
PMC8702989_02_OTT-14-5447-g0003.jpg
f0003
Immunohistochemistry showed GPC-3 (+), CK7 (-), CK19 (-), CD34 (vascular+) and MUC-1 (-) (Figure 3A). In March 2020, the patient discontinued CIK therapy due to the disease progressed (Figure 3B and C), and was respectively performed with interventional therapy in March and June 2020.
(A) Changes of imaging and (B) AFP before and after PD-1 treatment from August to December 2020.
OTT-14-5447-g0004.jpg
PMC8702989_02_OTT-14-5447-g0004.jpg
f0004
AFP level was reduced to 13.88 ng/mL. On December 26, 2020 (After using 4 cycle of PD-1), the efficacy was assessed as CR, AFP level was 3.38 ng/mL (Figure 4A and B). At present, the patient is still receiving sintilimab immunotherapy and with good tolerance.
PMC8702989_02
Changes of (A) right lobe lesions and (C) tumor markers during bi-specific antibody conjugated CIK treatment from February to December 2019. (B) The efficacy was assessed as CR after the patient injected with PD-1 and (D) Biomarker curve from April to October 2020.
OTT-14-5447-g0002.jpg
PMC8702989_02_OTT-14-5447-g0002.jpg
f0002
From October 2018 to March 2020, she was enrolled in the clinical trial "A Randomized, Controlled Phase II Clinical Study of Activated CIK Armed with Bispecific Antibody for Advanced Liver Cancer" (NTC03146637), and were treated with bi-specific antibody conjugated CIK Cells (GPC-3) for 4+4 cycles (Supplementary Figure 2).
(A) The pathological results showed that moderately differentiated of HCC. (B) Changes of AFP and (C) imaging before and after bi-specific antibody conjugated CIK treatment from October 2018 to March 2020. Red arrows pointed to target lesions and red circles marked non-target lesions.
OTT-14-5447-g0003.jpg
PMC8702989_02_OTT-14-5447-g0003.jpg
f0003
Immunohistochemistry showed GPC-3 (+), CK7 (-), CK19 (-), CD34 (vascular+) and MUC-1 (-) (Figure 3A). In March 2020, the patient discontinued CIK therapy due to the disease progressed (Figure 3B and C), and was respectively performed with interventional therapy in March and June 2020.
(A) Changes of imaging and (B) AFP before and after PD-1 treatment from August to December 2020.
OTT-14-5447-g0004.jpg
PMC8702989_02_OTT-14-5447-g0004.jpg
f0004
AFP level was reduced to 13.88 ng/mL. On December 26, 2020 (After using 4 cycle of PD-1), the efficacy was assessed as CR, AFP level was 3.38 ng/mL (Figure 4A and B). At present, the patient is still receiving sintilimab immunotherapy and with good tolerance.