Cancer-Testis Antigens in Triple-Negative Breast Cancer: Role and Potential Utility in Clinical Practice

Lam, Runyi Adeline; Tien, Tracy Zhijun; Joseph, Craig Ryan; Lim, Jimmy; Thike, Aye Aye; Iqbal, Jabed; Tan, Puay Hoon; Yeong, Joe

doi:10.3390/cancers13153875

Cited by 13 publications

(14 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These proteins are normally expressed in embryonic stem cells and testicular germ cells, minimally expressed in most other normal tissues but often expressed at high levels in many different tumors 60 . Several hundred CTAs have been identified, and many have served as targets in vaccination involving patients with TNBC 61 . Perhaps the most notable is cancer/testis antigen 1B (NY-ESO-1) 62 .…”

Section: Breast Cancer Vaccinesmentioning

confidence: 99%

Immunotherapy in breast cancer: an overview of current strategies and perspectives

et al. 2023

View full text Add to dashboard Cite

Recent progress in immunobiology has led the way to successful host immunity enhancement against breast cancer. In triple-negative breast cancer, the combination of cancer immunotherapy based on PD-1/PD-L1 immune checkpoint inhibitors with chemotherapy was effective both in advanced and early setting phase 3 clinical trials. These encouraging results lead to the first approvals of immune checkpoint inhibitors in triple-negative breast cancer and thus offer new therapeutic possibilities in aggressive tumors and hard-to-treat populations. Furthermore, several ongoing trials are investigating combining immunotherapies involving immune checkpoint inhibitors with conventional therapies and as well as with other immunotherapeutic strategies such as cancer vaccines, CAR-T cells, bispecific antibodies, and oncolytic viruses in all breast cancer subtypes. This review provides an overview of immunotherapies currently under clinical development and updated key results from clinical trials. Finally, we discuss the challenges to the successful implementation of immune treatment in managing breast cancer and their implications for the design of future clinical trials.

show abstract

Section: Breast Cancer Vaccinesmentioning

confidence: 99%

Immunotherapy in breast cancer: an overview of current strategies and perspectives

et al. 2023

View full text Add to dashboard Cite

show abstract

“…We analyzed T-cell responses to the antigens targeted by the infused line (NY-ESO-1, SSX2, MAGE-A4, Survivin, and PRAME) as well as against a range of other non-targeted BC-expressed antigens including MAGE-A1, -A2B, -A3, -C1, and WT1. 24 , 27 , 30 , 37 We reasoned that the detection of such cells might be indicative of an active antitumor effect mediated by the cells infused, producing in vivo antigen spreading, thereby enhancing the antitumor benefits of our therapy. As shown in Figure 2 , most patients who experienced disease progression exhibited either a decrease or a transient increase in tumor-specific T cells, which peaked within 8 weeks of infusion and subsequently declined.…”

Section: Resultsmentioning

confidence: 99%

“… 9 – 11 To address this issue and with the goal of developing an effective immunotherapy for BC, we developed a non-engineered T-cell product containing both CD4+ (helper) and CD8+ (cytotoxic) T cells with native TCR specificity for multiple TAAs. Our target antigens were chosen based on the frequency of expression in BC of all subtypes (PRAME: 27–97%; SSX family: 4–65%; MAGE-A4: 4–86%; NY-ESO-1: 8–64%; and Survivin: 26–96%) 16 – 28 , 30 , 37 and immunogenicity to T cells. 24 , 28 , 30 , 31 We hypothesized that the infusion of such multiTAA T cells would be safe and promote anti-BC activity, minimizing the risk for antigen-negative relapses.…”

Section: Discussionmentioning

confidence: 99%

“…From day 10 and weekly thereafter, responder T cells were restimulated with pepmix-pulsed DCs in the presence of IL-15 (5 ng/mL) or IL-2 (50-100 U/mL) until sufficient numbers were achieved for patient infusion and release testing. The resulting multiTAA T-cell lines were harvested at a median of 26 [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] days post-T-cell initiation.…”

Section: Generation Of Multitaa T Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer

et al. 2022

View full text Add to dashboard Cite

Purpose: Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC. Materials and methods: MultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally recurrent unresectable BC of all subtypes and infused at a fixed dose level of 2 × 107/m2. Patients received two infusions of cells 4 weeks apart and safety and clinical activity were determined. Cells were administered in an outpatient setting and without prior lymphodepleting chemotherapy. Results: All patients had estrogen receptor/progesterone receptor positive BC, with one patient also having human epidermal growth factor receptor 2-positive. There were no treatment-related toxicities and the infusions were well tolerated. Of the 10 heavily pre-treated patients enrolled and infused with multiTAA T cells, nine had disease progression while one patient with 10 lines of prior therapies experienced prolonged (5 months) disease stabilization that was associated with the in vivo expansion and persistence of T cells directed against the targeted antigens. Furthermore, antigen spreading and the endogenous activation of T cells directed against a spectrum of non-targeted tumor antigens were observed in 7/10 patients post-multiTAA infusion. Conclusion: MultiTAA T cells were well tolerated and induced disease stabilization in a patient with refractory BC. This was associated with in vivo T-cell expansion, persistence, and antigen spreading. Future directions of this approach may include additional strategies to enhance the therapeutic benefit of multiTAA T cells in patients with BC.

show abstract

“…NY-ESO-1 and XAGE-1B are one of the CTAs, which are a large family of tumor-associated antigens only in germ cells of the testis and placenta ( 12 , 13 ), and in various malignant tumors, such as melanoma ( 14 ), squamous cell carcinoma ( 15 ), non-small cell lung cancer ( 16 ), gastric cancer ( 17 ), hepatocellular carcinoma ( 18 ), breast cancer ( 19 ), ovarian cancer ( 20 ), bladder cancer ( 21 ), prostate cancer ( 22 ), multiple myeloma ( 23 ), synovial sarcoma ( 24 ), and Ewing’s sarcoma ( 25 ). CTAs can be divided into two groups, those that are encoded on the X chromosome (CT-X antigens) and those that are not (non-X CT antigens) ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

et al. 2023

View full text Add to dashboard Cite

Cutaneous angiosarcoma (CAS) is a highly malignant tumor with few effective treatments. Although the indication for immune checkpoint inhibitors such as anti-PD-1 antibodies is expected to expand, there are many unknowns regarding the tumor immune microenvironment in CAS, which is generally considered an immunologically “cold” tumor. Our previous study demonstrated that tertiary lymphoid structures (TLSs) were associated with a favorable prognosis in CAS. However, we still don’t know what the difference is between cases of TLS-rich and TLS-poor. Furthermore, the number of TLSs can vary significantly between lesions in the same case, for example, between primary and recurrence. To analyze the changes in the tumor immune microenvironment in CAS in more detail, we performed comprehensive RNA sequencing using a Next-generation sequencer (NGS). Sixty-two samples from 31 cases of CAS treated at Nagoya City University were collected. NGS and gene set enrichment analysis (GSEA) were performed on 15 samples among them. Immunohistochemistry and prognostic analysis by Kaplan-Meier method were performed on all 62 samples. NGS results showed that NY-ESO-1 (CTAG1B) was significantly upregulated in the TLS-positive cases. Immune checkpoint molecules including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) were upregulated in TLS-negative or TLS-low cases and seemed to associate with the suppression of TLS formation. In a comparison of primary and recurrent lesions, other cancer-testis antigens (CTAs) including XAGE-1B were significantly upregulated in recurrent lesions. The number of infiltrating CD8-positive cells and TLSs showed no significant trend between primary and recurrent lesions. However, the PD-L1 expression of tumor cells was significantly lower in recurrent than in primary lesions. Chemokines correlated with NY-ESO-1 expression were CCL21 and CXCL8, and only CCL21 correlated with the number of TLS. There was no chemokine associated with XAGE-1. NY-ESO-1 and XAGE-1 are detectable by immunohistochemistry. Although each cannot be a prognostic marker by itself, they can be a helpful marker in combination with the number of TLSs. CTAs play an essential role in forming the tumor immune microenvironment in CAS. These findings are evidence that CAS is an immunologically “hot” tumor and provides us with potential therapeutic targets and encourages the expansion of immunotherapy indications.

show abstract

Cancer-Testis Antigens in Triple-Negative Breast Cancer: Role and Potential Utility in Clinical Practice

Cited by 13 publications

References 111 publications

Immunotherapy in breast cancer: an overview of current strategies and perspectives

Immunotherapy in breast cancer: an overview of current strategies and perspectives

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

Contact Info

Product

Resources

About