Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection

Pan, Qiuzhong; Zhao, Jingjing; Yang, Chih Ping; Zhou, Yuqing; Lin, Junzhong; Tang, Yan; Gu, Jianyou; Wang, Qi-Jing; Li, Yongqiang; He, Jia; Chen, Shiping; Song, Mengjia; Huang, Yue; Yang, Jin-Hao; Weng, Desheng; Xia, Jianchuan

doi:10.1080/2162402x.2020.1752563

Cited by 16 publications

(46 citation statements)

References 39 publications

(49 reference statements)

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“…Apart from single and combined therapies, the sequential use of chemotherapy, radiotherapy, targeted therapy followed by immunotherapy has been emerging as one of the latest choices in cancer treatment and proved to be more effective than immunotherapy alone by some previous study in lung cancer, colorectal cancer, hepatocellular carcinoma, and cholangiocarcinoma (13)(14)(15)(16)(17). However, the sequential use of chemotherapy and immunotherapy in osteosarcoma has never been reported, and only in vitro evidence became available very recently, showing that checkpoint blockade in combination with doxorubicin augments tumor cell apoptosis (18), and neoadjuvant chemotherapy reprogrammed the tumor immunologic microenvironment and facilitated the subsequent immunotherapy in osteosarcoma (19).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Sequential Chemotherapy and Immunotherapy Produce Sustained Response in Osteosarcoma With High Tumor Mutational Burden

et al. 2021

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BackgroundImmunotherapy has provided an effective method for the treatment of many cancers. However, its efficacy in osteosarcoma is not satisfactory so far.Case PresentationHere, we presented a case of osteosarcoma treated with sequential chemotherapy and immunotherapy and showed promising therapeutic potential. The 29-year-old female patient presented 9th rib osteosarcoma with suspected right lung lower lobe metastasis. Surgery was performed to remove the primary lesion, and a series of chemotherapies were given afterward in consideration of the response and tolerance. The right lung lower lobe metastasis was under control first but progressed (PD) 9 months after the initiation of therapy. The lesion was surgically removed and subsequent chemotherapy was implemented. The patient had good tolerance with chemotherapy and maintained well for approximately 11 months before the discovery of 11th rib and right lung upper lobe metastases. Surgery was then performed on both lesions and achieved complete response. Post-surgical brief chemotherapy and subsequent long-term immunotherapy (pembrolizumab) maintained continuous remission for 33 months. The patient survived for 60 months with well-controlled disease from the time of confirmed diagnosis. Genetic alterations of all primary and metastatic lesions were investigated by whole-exome sequencing (WES). Substantial similarity in mutational landscape between the primary lesion and 11th rib metastasis and between the two lung metastases were revealed, while substantial heterogeneity was found between the rib lesions and lung metastases. The tumor mutational burden (TMB) for the 9th rib primary lesion, the metastatic 11th rib lesion, and the metastatic right upper and lower lobe nodule tissues was 8.02, 2.38, 4.61, and 0.14 mutations/Mb, respectively. The primary lesion exhibited the most diverse copy number variation (CNV) changes among all lesions. Furthermore, pathway enrichment analysis also suggested significant heterogeneity among the lesions.ConclusionsSurgery with sequential chemotherapy and maintenance immunotherapy was shown to have good response for the first time on osteosarcoma patient who had high TMB tumor lesions and good tolerance for chemotherapy and immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Case Report: Sequential Chemotherapy and Immunotherapy Produce Sustained Response in Osteosarcoma With High Tumor Mutational Burden

et al. 2021

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Section: Cell Therapy Strategies For Crc Treatmentmentioning

confidence: 99%

“…The cytokine-induced killer (CIK) cells, a frequently studied cell immunotherapy in CRC, are a heterogeneous group of cells obtained from peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with an anti-CD3 antibody and a cocktail of cytokines [ 17 , 18 , 19 ]. These cells share functional and phenotypic properties with NK and T cells and are characterised by rapid expansion ex vivo, non-major histocompatibility complex (MHC)-restricted tumour-killing activity, strong antitumour activity and minimal toxicity [ 17 , 18 ]. It has been observed that the combination of adjuvant chemotherapy with sequential infusions of CIK cells significantly improved the progression-free survival (PFS), disease-free survival (DFS) and OS rates of CRC patients [ 18 , 19 ], especially in those with high-risk T4 stage and insufficient duration of chemotherapy (DFS and OS) [ 18 ].…”

Section: Cell Therapy Strategies For Crc Treatmentmentioning

confidence: 99%

“…These cells share functional and phenotypic properties with NK and T cells and are characterised by rapid expansion ex vivo, non-major histocompatibility complex (MHC)-restricted tumour-killing activity, strong antitumour activity and minimal toxicity [ 17 , 18 ]. It has been observed that the combination of adjuvant chemotherapy with sequential infusions of CIK cells significantly improved the progression-free survival (PFS), disease-free survival (DFS) and OS rates of CRC patients [ 18 , 19 ], especially in those with high-risk T4 stage and insufficient duration of chemotherapy (DFS and OS) [ 18 ]. Moreover, this combination therapy has also been used on mCRC patients, showing good tolerability and a significant increase in OS [ 20 ].…”

Section: Cell Therapy Strategies For Crc Treatmentmentioning

confidence: 99%

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Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells

Aparicio

Belver

Enríquez

et al. 2021

IJMS

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Colorectal cancer (CRC) is a global public health problem as it is the third most prevalent and the second most lethal cancer worldwide. Major efforts are underway to understand its molecular pathways as well as to define the tumour-associated antigens (TAAs) and tumour-specific antigens (TSAs) or neoantigens, in order to develop an effective treatment. Cell therapies are currently gaining importance, and more specifically chimeric antigen receptor (CAR)-T cell therapy, in which genetically modified T cells are redirected against the tumour antigen of interest. This immunotherapy has emerged as one of the most promising advances in cancer treatment, having successfully demonstrated its efficacy in haematological malignancies. However, in solid tumours, such as colon cancer, it is proving difficult to achieve the same results due to the shortage of TSAs, on-target off-tumour effects, low CAR-T cell infiltration and the immunosuppressive microenvironment. To address these challenges in CRC, new approaches are proposed, including combined therapies, the regional administration of CAR-T cells and more complex CAR structures, among others. This review comprehensively summarises the current landscape of CAR-T cell therapy in CRC from the potential tumour targets to the preclinical studies and clinical trials, as well as the limitations and future perspectives of this novel antitumour strategy.

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“…Adoptive immunotherapy based on genetic engineering of lymphocytes to create chimeric antigen receptormodi ed T (CAR-T) cells has become one of the most promising approaches in the eld of cancer therapy [3]. Several groups have reported preclinical studies in which CRC was treated using CAR-T cells, such as targeting epidermal growth factor receptor-(EGFR-) [4], EpCAM [5] and EGP40 [6] CAR T cells and targeting carcinoembryonic antigen (CEA) CAR cytokine-induced killer (CIK) cells [7]. In addition to preclinical studies, clinical trials using CAR-T cells targeting HER2 [8], TAG-72 [9], CEA [10] and CEACAM5 [11] have also been conducted in patients with CRC.…”

Section: Introductionmentioning

confidence: 99%

Inducible secreting TLR5 agonist CBLB502 enhances antitumor activity of CAR133-NK92 cells for colorectal cancer

2022

Preprint

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CAR-T/NK cells have been used with minimal success against solid malignancies such as colorectal cancer (CRC) in part because of the heterogeneous nature of tumour-associated antigens and the emergence of antigen loss variants that lead to negative antigen relapses after the initial response. Here, we firstly engineered a CAR133-NK92 cells with inducible secretion of TLR5 agonist CBLB502 at the tumour site, and demonstrated that CAR133-i502-NK92 cells in vitro exhibit enhanced proliferation, cytokines expression and antitumor activities compared with CAR133-NK92 cells. In addition, CAR133-i502-NK92 cells has more potent antitumor activities not only for hCD133+ but also hCD133+/hCD133- mixed colon cancer xenograft mouse models, and also has well tolerated in vivo. Notably, CBLB502 secreting from CAR133-i502-NK92 cells can effectively activate endogenous immune cells to eradicate tumor cells. Taken together, our study demonstrates that the CAR133-i502-NK92 cells not only specific directly eliminate CD133 positive colon cancer cells in a CAR133-dependent manner, but also can indirectly eradicate CD133 negative heterogeneous colon cancer cells in an CBLB502-elicted endogenous immune activation manner, which might offer a promising therapeutic new strategy for colorectal cancer.

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Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection

Cited by 16 publications

References 39 publications

Case Report: Sequential Chemotherapy and Immunotherapy Produce Sustained Response in Osteosarcoma With High Tumor Mutational Burden

Case Report: Sequential Chemotherapy and Immunotherapy Produce Sustained Response in Osteosarcoma With High Tumor Mutational Burden

Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells

Inducible secreting TLR5 agonist CBLB502 enhances antitumor activity of CAR133-NK92 cells for colorectal cancer

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