Cancer Research and Treatment

Gastrointestinal cancer

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer: Keun-Wook Lee, Sae-Won Han, Tae Won Kim, Joong Bae Ahn, Ji Yeon Baek, Sang Hee Cho, Howard Lee, Jin Won Kim, Ji-Won Kim, Tae-You Kim, Yong Sang Hong, Seung-Hoon Beom, Yongjun Cha, Yoonjung Choi, Seonhui Kim, Yung-Jue Bang; Cancer Res Treat. 2024;56(2):590-601. Published online December 7, 2023; DOI: https://doi.org/10.4143/crt.2023.1117

Abstract PDF Supplementary Material PubReader ePub

Purpose
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m²; leucovorin 400 mg/m²; 5-fluorouracil 400 mg/m² bolus and 2,400 mg/m² infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

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Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef

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Development of a New Nonoclonal Antibody CC5 Using a Cervical Carcinoma Cell-line Derived From Korean Woman: Jin Woo Kim, Chun Ok Seo, Eun Young Cho, Heung Kee Kim, Sa Jin Kim, Soo Young Hur, Young Wook Kim, Tae Chul Park, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1999;31(3):562-574.

Abstract PDF: PURPOSE
Cancer of the uterine cervix remains the leading cause of cancer death in Korean women. Conventional examinations still have limitations with regards to sensitivity and specificity in diagnosis and to monitoring of the disease. Thus, an additional specific tumor marker is needed for early detection of recunence of uterine cervical carcinoma and for estimation of prognosis.
MATERIALS AND METHODS
Monoclonal antibodies against human cervical carcinoma were generated using hybridoma technology. These tnurine monoclonal antibodies were produced by fusion of spleen cells obtained from mice immunized with CUMC-6, a human cell line of squamous cell carcinoma derived from uterine cervix, and P3-X63-Ag8 mouse myeloma cells.
RESULTS
We obtained 415 hybridomas secreting specific monoclonal antibodies to cervical carcinoma antigen continuously. Among them, one hybridoma designated CCS that was highly reactive with cervical carcinoma was selected and examined on. the staining pattern and the reactivity with antigenic detenninants of cervical carcinoma. Immunohistochemical staining revealed that CCS monoclonal antibody reacted with all of the seven cervical carcinoma tissues, but also reacted with one of the ten (10%) normal cervical tissues. Westem blot analysis showed that CC5 monoclonal antibody detected single 19.5-kDa protein band in cervical cancer patient's sera. The detection rate was 88% (7/8). However, the antibody did not show any reactivity to 15 sera of normal healthy women tested. Sodium dodecyl sulfate polyacrylamide gel electrophoretic (SDS-PAGE) analysis of CCS monoclonal antibody immunoprecipitates of extracts of L-[S] methionine-labeled human cer vical carcinoma cells showed a major band in apparent molecular weight of 51,000 daltons. The isotype and subclass of CC5 monoclonal antibody was IgG2b in hemagglutination assay.
CONCLUSIONS
We have developed a new monoclonal antibody, CC5, against squamous cell carcinoma of the human uterine cervix. Further investigation is needed to establish this monoclonal antibody as an immunodiagnostic devise for cervical cancer.

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Expressions of Blood Group Antigen A in Lung Cancer: Pyo Seong Han, Suk Chul Hong, Jong Jin Lee, Hai Jung Cho, Ae Kyung Kim, Ju Ock Kim, Sun Young Kim; J Korean Cancer Assoc. 1994;26(5):770-778.

Abstract PDF: Background
Blood group anti#gens A, B, and H, identical with those present in erythrocytes, are also found in some normal tissues. The expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms. Variability of blood group antigen expression among tumor cells is a potentially useful indicator of functional tumor cell heterogeneity or progression. We evaluated the prognostic value of expression of blood group antigen A as a prognostic factors. Method: This study analyzed the expressions and losses of blood group antigen A in lung cancer patients with blood type A or AB. The presence of blood-group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 30 patients who underwent curative surgery, bronchoscopic biopy, percutaneous needle biopsy, lymph node biopsy for diagnosis of lung cancer from 1991 through 1994. Results; 1) The expression of blood group isoantigen A was observed in 15 cases (50%) 2) The expression of blaod group isoantigen A was observed in 64% of stage II, 47% of stage III, 25% of stage IV. 3) The expression of blood group isoantigen A was observed in 0% of large cell carcinoma, 17 % of small cell carcinoma, 63% of squamous cell carcinoma, 50% of adenocarcinoma, 100% of bronchioloalveolar cell carcinoma. 4) The losses of blood group isoantigen A were observed in 67% of patient who survived below 1 year, 44% of patients who survived 1 to 2 years, but no loss of expression were observed in patients who survived more than 2 years. 5) The median survival times of expressed group and lossed group of isoantigen A were 16.0, 9.8 months, respetively. 6) The loss of blood group antigen A was higher in patients who had metastatic lymph nade than in patients who had not. Conclusion: the expression of blood group antigen A in cancer cells is important favorable prognostic factor in patients with lung cancer.

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Cyto - Melecular Conparison between Primary Squamous Cell Line from Bladder: Joong Shin Kang, Soo Sang Sohn, Dage Kwang Kim, Sung Ik Chang; J Korean Cancer Assoc. 1995;27(1):111-121.

Abstract PDF: To evaluate which cyto-molecular genetic evolutionary patterns take place during the in vitro establishment of permanent squamous cell carcinoma cell line of urinary bladder, cytomolecular genetic follow up was performed on primary culture for two weeks and on cancer cell line after contineued culture for three years in vitro. Near-diploid cells present on primary culture and near-hypertriploid or hypotetraploid cells, in contrast, present on cancer cell line. Chromosomal gains or losses are random from primary cancer to cell line. There are two kinds af structural cytogenetic abnormalities through progress in culture time. One is maintaining abnormal clone from original cancer to derived cancer cell line. Others are cytogenetic alteration during progessing culture time; Increasing and decreasing abnormal clones are coexisted in both grouy. Activation of oncogenes are different from primary cancer to cancer cell line. In conclusion, there are genetic alterations through progressing from primary cancer to cancer cell line. Due to these alterations, cancer ce11 1ines don't substituted for primary cancer and can not be availabe for using materials to choose production on monoclonal antibody and theraputic test.

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A Monocolnal Antibody P1 Against Leukocyte Common Antigen: Kyeong Cheon Jung, Sang Yoon Kim, Cheung Seog Park, Seong Hoe Park, Sang Kook Lee; J Korean Cancer Assoc. 1995;27(1):121-130.

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A Study of the Runctional and Biochemical Charcteristics and Antigenic Expression of Hematopoietic Cells Using Monoclonal Antibodies to a Thymocyte Surface Antigen: Cheung Seog Park, Seong Hoe Park, Myung Hwan Cho; J Korean Cancer Assoc. 1995;27(2):331-340.

Abstract PDF: In order to investigate functional variation of antigenic epitopes and expression patterns of hematopoietic cells and biachemical characteristics, we produced murine monoclonal antibodies, anti-YG 14 and anti-YG 15, against human thymocytes. We found that these monoclonal antibodies recognized same surface molecule which has been confirmed by immuno-precipitation analysis. This antigen was expressed in peripheral monocytes, subset of T cells, platelets, and epidermis of skin, but not expressed in granulocytes and peripheral B cells. It was approximately 24KDa protein in malecular weight and expressed as monomer. Its expression patterns and biochemical characteristics were similar to those of leukocyte differntiation antigen, CDB. With blocking test, we found out that YG14, YG15 monoclonal antibodies recognized different epitopes of same molecule, using flow cytometry. With the results of colony forming assay, it is very intriguing to see that YG15 monoclonal antibody showed increased colony forming activity but the YG14 monoclonal antibody did not. These results strongly suggest that engagement of different epitopes of same molecule can show different functional activity.

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Radioimmunotherapy for Lung Metastasis of MMTV-induced Breast Cancer in Mice with 131I-labeled Monoclonal Antibody: Sang Kyun Sohn, Jae Tae Lee, Chang Woon Choi, Tibor Bakacs, M . Belen Moreno, Byeong Cheol Ahn, Kyu Bo Lee, David Segal, Chang H . Paik; J Korean Cancer Assoc. 1996;28(3):472-483.

Abstract PDF: Radiolabeled monoclonal antibodies appear to be gaining a role in the management of cancer by means of imaging methods to detect sites of increased radioactivity, and several products have been developed and tested clinically. In the area of radioimmunotherapy, the radiolabeled monoclonal antibodies have shown the potentials in the treatment of the microtumors and metastases due to its inherited benefit from bystander effect of the ionizing radiation delivered with radioimmunoconjugates. We have evaluated the antitumor effects of I-131 labeled P2AE12 antibody, prepared against glycopratein of gp52 MMTV-induced murine mammary tumor cell, in allogeneic model of pulmonary metastatic cancer. The BALB/c normal mice were injected intravenously with 5 x 10(5) murine breast cancer cells and pulmonary metastases were acauired in all mice. Three days and ten days after tumor cell injection, each set of 250uCi of I-131 labeled antibody was injected in 15-20 mice for one or two treatment group. Survival of treatment group was compared with that of control group. One-treatment resulted in prolonged median survival of mice bearing metastases from 14(range: 13-16 days) to 16 days(range: 1422days), and two-treatments to 22(range: 20 to more than 40 days) days. Treatment with I-131 labeled P2AE12, antibody resulted in marked reduction of tumor burden in lung sections taken on days 7 and 14 days. Our results showed that radiolabeled monoclonal antibody can inhibit the growth of allogeneic solid tumor metastases in mice. Although it did not cure these kinds of aggressive metastatic tumors, these findings encourage the further evaluation of the radioimmunotherapy in pulmonary metastases with different schemes to enhance tumor uptake of radiolabeled antibody, as well as lessen the uptake in normal tissue.

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Growth Activity of Thyroid Neoplasia Estimated by Immunohisochemical Procedure Usang Monoclonal Antibody MIB-1: Dae Young Lee, Hong Jo Choi, Sang Soon Kim, Sun Kyung Lee; J Korean Cancer Assoc. 1996;28(4):655-665.

Abstract PDF: To increase our knowledge of the basic biological mechanisms of thyroid lesions, growth activity(GA) in 63 thyroid tumors was evaluated by immunohistochemical stain using monoclonal antibody MIB-1 which represents growth activity bi its positive cell rates. The results obtained were summarized as follows. The MIB-1 positive cell rate of normal tissue(0.18%) was very low and significantly lower than that of follicular adenoma(1.91%). The MIB-1 positive cell rate of thyroid carcinomas was significantly higher than that of follicular adenoma or normal tissue. Of the thyroid carcinomas, the highest MIB-1 positive cell rate was observed in undifferentiated carcinoma(29.33%), followed by follicular carcinoma(8.95%), medullary carcinoma(8.16%), papillary carcinoma(3.54%) in order their MIB-1 positive cell rate. Statistically significant differences of MIB-1 pasitive cells were noted among various types of thyroid carcinomas with two exceptions between medullary carcinoma and papillary carcinoma, or between medullary carcinoma and follicular carcinama. Of the follicular tumors, the MIB-1 positve cell rate was obserbed in 12.40% of widely invasive follicular carcinoma, in 5.89% of minimally invasive follicular carcinoma, in 3.26% of solid/trabecular adenoma, and in 0.90% of normo/macrofollicular adenoma. Significant difference of MIB-1 positive cell rate were found between various subtypes of follicular tumors. In papillary tumors, the MIB-l positive cell rate of overt papillary carcinoma(5.32%) was significantly higher than that of occult papillary carcinoma(1.25%). Our findings suggest that immunohistochemical evaluation using the antibody MIB-1 contributes to the understanding of growth characteristics and biological activities in thyroid tumors.

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