A combination of telomerase inhibition and NK cell therapy increased breast cancer cell line apoptosis

Mazloumi, Zeinab; Rafat, Ali; Asl, Khadijeh Dizaji; Charoudeh, Hojjatollah Nozad

doi:10.1016/j.bbrc.2022.11.090

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…Combining the traditional cancer treatment of radiotherapy with immunotherapy can produce synergistic effects because of the specific interaction between the immune system and radiation [ 81 , 82 ]. A recent in vitro study has shown that a combination of telomerase inhibition and NK cell therapy increased breast cancer cell line apoptosis [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy

Bashraheel

Goda

2023

IJMS

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Bacterial superantigens (SAgs) are effective T-cell stimulatory molecules that lead to massive cytokine production. Superantigens crosslink between MHC class II molecules on the Antigen Presenting Cells (APC) and TCR on T-cells. This enables them to activate up to 20% of resting T cells, whilst conventional antigen presentation results in the activation of 0.001–0.0001% of the T cell population. These biological properties of superantigens make them attractive for use in immunotherapy. Previous studies have established the effectiveness of superantigens as therapeutic agents. This, however, was achieved with severe side effects due to the high lethality of the native toxins. Our study aims to produce superantigen-based peptides with minimum or no lethality for safer cancer treatment. In previous work, we designed and synthesized twenty overlapping SPEA-based peptides and successfully mapped regions in SPEA superantigen, causing a vasodilatory response. We screened 20 overlapping SPEA-based peptides designed and synthesized to cover the whole SPEA molecule for T-cell activation and tumor-killing ability. In addition, we designed and synthesized tumor-targeted superantigen-based peptides by fusion of TGFαL3 either from the N′ or C′ terminal of selected SPEA-based peptides with an eight-amino acid flexible linker in between. Our study identified parts of SPEA capable of stimulating human T-cells and producing different cytokines. We also demonstrated that the SPEA-based peptide conjugate binds specifically to cancer cells and can kill this cancer. Peptides induce T-cell activation, and tumor killing might pave the way for safer tumor-targeted superantigens (TTS). We proposed the combination of our new superantigen-based peptide conjugates with other immunotherapy techniques for effective and safer cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy

Bashraheel

Goda

2023

IJMS

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“…Among these, BIBR1532 has received significant attention in recent years. Studies have demonstrated its synergistic effects in combination with NK cell therapy [ 167 ], paclitaxel [ 168 ], and arsenic trioxide [ 169 ].…”

Section: Therapeutic Potential Of Htert As a Target For Breast Cancermentioning

confidence: 99%

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer

Yang,

Han,

Guan

et al. 2023

Cell Commun Signal

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Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation of hTERT, observed in over 90% of tumors, plays a significant role in tumor initiation and progression. An in-depth exploration of hTERT activation mechanisms in cancer holds promise for advancing our understanding of the disease and developing more effective treatment strategies. In breast cancer, the expression of hTERT is regulated by epigenetic, transcriptional, post-translational modification mechanisms and DNA variation. Besides its canonical function in telomere maintenance, hTERT exerts non-canonical roles that contribute to disease progression through telomerase-independent mechanisms. This comprehensive review summarizes the regulatory mechanisms governing hTERT in breast cancer and elucidates the functional implications of its activation. Given the overexpression of hTERT in most breast cancer cells, the detection of hTERT and its associated molecules are potential for enhancing early screening and prognostic evaluation of breast cancer. Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for breast cancer treatment. These methods are also discussed in this paper.

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“…Several studies have demonstrated the synergistic effects of telomerase inhibitors along with NK cell-based therapy, paclitaxel, and arsenic trioxide. 16–18 …”

Section: Introductionmentioning

confidence: 99%

“…Several studies have demonstrated the synergistic effects of telomerase inhibitors along with NK cell-based therapy, paclitaxel, and arsenic trioxide. [16][17][18] In this study, we aimed to determine whether the antitumor response and quality of life were improved by administering GV1001 to patients with breast cancer who were undergoing treatment or could not proceed with aggressive treatment.…”

Section: Introductionmentioning

confidence: 99%

Retrospective Analysis of the Clinical Characteristics of Patients with Breast Cancer Treated with Telomerase Peptide Immunotherapy Combined with Cytotoxic Chemotherapy

Kim,

Yang,

Kim

et al. 2023

BCTT

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Purpose Telomerase activation, a critical step in cancer progression, occurs in approximately 95% of breast cancer cases. Telomerase is an attractive therapeutic target for breast cancer owing to its unique expression pattern. GV1001, a telomerase-derived peptide, is loaded onto human leukocyte antigen (HLA) class II antigen-presenting cells and binds to CD4+ T cell activating immune responses. This study aimed to evaluate the effectiveness and safety of co-administration of GV1001 and cytotoxic chemotherapy in patients with heavily-treated metastatic breast cancer. Patients and methods We analyzed 63 patients with breast cancer who received both GV1001 and cytotoxic chemotherapy. The GV 1001 administration methods involves 0.56 mg intradermal injection three times during the first week, one time at weeks 2, 3, 4, and 6, and then once every 28 days. The primary endpoint of this study was quality of life according to EORTC QLO-C30 and EQ-5D, while the secondary endpoint was the antitumor response according to RECIST 1.1, progression-free survival, overall survival, and toxicity profile. Results In 34 patients with HR+ breast cancer evaluable for tumor response, the disease control rate (DCR) and overall response rate (ORR) were 58.8% and 26.4%, respectively. The DCR and ORR were 66.6% and 28.5% in 21 patients with HER-2+ and 50% and 25% in patients with triple-negative breast cancer (TNBC), respectively. The median progression free survival was 10.4, 8.7, and 5.6 months in HR+, HER-2+, TNBC, respectively. The overall survival was 19.7, 13.2, and 9.4 months for patients with HR+, HER-2+, and TNBC, respectively. Most patients had an improved quality of life with statistically significant differences in some variables. The patients in this study experienced no additional toxicities other than the cytotoxic chemotherapy-associated side effects. Conclusion GV1001 is a relatively safe anticancer vaccine for patients with heavily-treated breast cancer and can to improve the quality of life.

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A combination of telomerase inhibition and NK cell therapy increased breast cancer cell line apoptosis

Cited by 6 publications

References 31 publications

Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy

Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer

Retrospective Analysis of the Clinical Characteristics of Patients with Breast Cancer Treated with Telomerase Peptide Immunotherapy Combined with Cytotoxic Chemotherapy

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