Combination of DC/CIK adoptive T cell immunotherapy with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients: a prospective patients’ preference-based study (PPPS)

Zhao, Yanhua; Wang, Xiaoli; Song, Yang; Zhou, Xinna; Jiang, Ni; Zhou, Lei; Huang, Hongyan; Zhao, Jiaju; Morse, Michael A.; Hobeika, Amy; Ren, Jun; Lyerly, H. Kim

doi:10.1007/s12094-018-1968-3

Cited by 35 publications

(28 citation statements)

References 35 publications

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“…Indeed, in the current case, no expression of either PD-1 or PD-L was identi ed in tumor biopsies. Studying an alternative form of immunotherapy, we have previously reported that infusions of mixtures of dendritic cells and cytokine induced killer cells (DC-CIK) demonstrated e cacy in several solid tumor malignancies [9,10,14,[20][21][22]. We designed an N-of-1 study to characterize the changes in immune cell pro les of a patient with NMIBC who refused radical cystectomy and instead opted to participate in a study of immunotherapy with DC-CIK after completing standard interventions.…”

Section: Discussionmentioning

confidence: 99%

Serial Assessment of Circulating T lymphocyte Phenotype and Receptor Repertoire During Treatment of Non-Muscle Invasive Bladder Cancer with Adoptive T Cell Immunotherapy

Wang

Jiang

Morse

et al. 2020

Preprint

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Background: Recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) are frequent despite intravesical therapy. We hypothesized that administration of an activated T cell immunotherapy (ACT) at times when immunosuppressive populations were noted to have increased in peripheral blood would prevent recurrence of disease.Method: This was an N-of-1 study. A subject with multiple primary bladder high grade urothelial carcinomas who had initially completed standard resection and chemotherapy was enrolled. ACT consisted of dendritic cells mixed with cytokine induced killer cells (DC/CIK)) which were infused intravenously 18 times over a 6 year period in response to observed increases in peripheral blood immunosuppressive CD8+/CD28- cells. Peripheral blood was analyzed for T cell phenotype by flow cytometry, T cell receptor (TCR) repertoire, and circulating tumor DNA (ctDNA) by next generation sequencing (NGS) at the time of each infusion. Standard of care cystoscopy and pelvic CT scans have been performed at routine intervals. Results: The patient’s resected bladder tumors did not express PD-1 or PD-L1. There has been no recurrence of urothelial carcinoma. Peripheral blood cytotoxic T cells and unique TCR clones increased and suppressive T cell populations decreased after DC/CIK infusions. ctDNA detected mutations in six tumor relevant genes (ARID1B, MYCN, CDH23, SETD2, NOTCH4 and FAT1) at baseline but all of them disappeared after the DC-CIK infusions.Conclusion: DC/CIK infusions were associated with beneficial changes in T cell phenotype, TCR repertoire, decreases in circulating tumor DNA and sustained recurrence-free survival.

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Section: Discussionmentioning

confidence: 99%

Serial Assessment of Circulating T lymphocyte Phenotype and Receptor Repertoire During Treatment of Non-Muscle Invasive Bladder Cancer with Adoptive T Cell Immunotherapy

Wang

Jiang

Morse

et al. 2020

Preprint

Self Cite

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“…All statistical evaluations were carried out using SPSS software (Statistical Package for the Social Science, version 15.0, SPSS Inc.) and GraphPad Prism 5 (Version 5.01, GraphPad Software, Inc.). A value of P < 0.05 was considered to be statistically significant in all the analyses (21,29).…”

Section: Discussionmentioning

confidence: 99%

“…In this study we have continuously validated the patient allocation design termed as the prospective patient's preference-based study (PPPS) in which the prospective assignment of patients with similar demographic characteristics to treatment cohorts is based on the patients' preference after complete communications and understandings of each possible accessible therapeutic option by the investigators, as we described in our previous studies (21,29). Both the research documentation and progress were approved and supervised by institutional review board (IRB).…”

Section: Study Design and Participantsmentioning

confidence: 99%

Autologous Dendritic Cell-Cytokine Induced Killer Cell Immunotherapy Combined with S-1 Plus Cisplatin in Patients with Advanced Gastric Cancer: A Prospective Study

Qiao

Wang

Zhou

et al. 2019

Clinical Cancer Research

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Purpose: We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer (AGC) and the role of mutational analysis of circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire in predicting clinical outcomes. Patients and Methods: Consecutive patients (n ¼ 63) with AGC were allocated to treatment with S-1 alone, S-1 plus cisplatin, DC-CIK combined with S-1 or DC-CIK combined with S-1 plus cisplatin. The primary endpoints were progression-free survival (PFS) and overall survival (OS) at 1 year; the secondary endpoints were disease control rate and analysis of ctDNA and TCR repertoire. Results: The DC-CIK infusions were well tolerated with no serious adverse events. The disease control rates (CR þ PR þ SD) were 5.6%, 33.3%, 47.1%, and 76.9% in the S-1 alone, the S-1 plus cisplatin, DC-CIK combined with S-1 and DC-CIK combined with the S-1 plus cisplatin groups, respectively (P ¼ 0.001). After adjusting for competing risk factors, treatment with DC-CIK combined with S-1 plus cisplatin was confirmed to be an independent predictor of PFS and OS (P ¼ 0.001). A decrease in the frequency and number of mutations in ctDNA was observed in 19 patients (63.3%) following the DC-CIK infusions. Decreased ctDNA mutational frequency and restored TCR repertoire were associated with improved PFS and OS (P ¼ 0.001). Conclusions: DC-CIK combined with S-1 plus cisplatin provided a favorable PFS and OS in patients with AGC and the combination therapy was safe with tolerable toxicities. Clinical efficacy correlated with decreases in ctDNA mutational profiles and restored TCR repertoire.

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“…Liu presented new findings from two separate groups on the critical roles of IL-1 receptor (IL-1R) and granulocytemacrophage colony-stimulating factor (GM-CSF) in CRS and ICANS, providing a rationale to block the IL-1R pathway using the IL-1R antagonist, Anakinra [82,83], and to neutralize GM-CSF, in order to control and prevent CRS and ICANS during CAR-T treatment [84]. [85,86]. Correlation of immunological biomarkers with clinical efficacy and clonal diversity of the TCRβ repertoires was reported [87].…”

Section: Fast and Furious Development Of Cell Therapymentioning

confidence: 99%

Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy

et al. 2020

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Cancer immunotherapy has reached a critical point, now that immune checkpoint inhibitors and two CART products have received market approval in treating 16 types of cancers and 1 tissue-agnostic cancer indication. Accompanying these advances, the 2018 Nobel Prize was awarded for the discovery of immune checkpoint pathways, which has led to the revolution of anti-cancer treatments. However, expanding the indications of immuno-oncology agents and overcoming treatment resistance face mounting challenges. Although combination immunotherapy is an obvious strategy to pursue, the fact that there have been more failures than successes in this effort has served as a wake-up call, placing emphasis on the importance of building a solid scientific foundation for the development of next-generation immuno-oncology (IO) agents. The 2019 China Cancer Immunotherapy Workshop was held to discuss the current challenges and opportunities in IO. At this conference, emerging concepts and strategies for IO development were proposed, focusing squarely on correcting the immunological defects in the tumor microenvironment. New targets such as Siglec-15 and new directions including neoantigens, cancer vaccines, oncolytic viruses, and cytokines were reviewed. Emerging immunotherapies were discussed in the areas of overcoming primary and secondary resistance to existing immune checkpoint inhibitors, activating effector cells, and targeting immunosuppressive mechanisms in the tumor microenvironment. In this article, we highlight old and new waves of IO therapy development, and provide perspectives on the latest momentum shifts in cancer immunotherapy.

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Combination of DC/CIK adoptive T cell immunotherapy with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients: a prospective patients’ preference-based study (PPPS)

Cited by 35 publications

References 35 publications

Serial Assessment of Circulating T lymphocyte Phenotype and Receptor Repertoire During Treatment of Non-Muscle Invasive Bladder Cancer with Adoptive T Cell Immunotherapy

Serial Assessment of Circulating T lymphocyte Phenotype and Receptor Repertoire During Treatment of Non-Muscle Invasive Bladder Cancer with Adoptive T Cell Immunotherapy

Autologous Dendritic Cell-Cytokine Induced Killer Cell Immunotherapy Combined with S-1 Plus Cisplatin in Patients with Advanced Gastric Cancer: A Prospective Study

Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy

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