Telomerase and CD4 T Cell Immunity in Cancer
Abstract
:1. Introduction
2. TERT and Cancer
3. TERT-Specific CD4 Th1 Cells as Pivotal Modulator of the Anti-Tumor Immune Response
3.1. Current MHC-II Restricted TERT Peptides
3.2. Prognostic Value of Systemic Anti-TERT CD4 T Cell Immunity in Cancer
3.3. Past and Current Therapeutic Approaches Targeting Anti-TERT CD4 Th1 Cell Immunity
4. Prospects for the Identification of Novel Immunogenic TERT CD4 Epitopes
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Peptide | Position | Sequence | Main HLA Restriction | Year | Ref. |
---|---|---|---|---|---|
p68 | TERT68-82 | APSFRQVSCLKELVA | HLA-DR | 2018 | [108] |
p911 1 | TERT911-927 | DEALGGTAFVQMPAH | HLA-DP4 | 2016 | [107] |
UCP1 | TERT44-58 | PAAFRALVAQCLVCV | HLA-DR | 2012 | [105,113] |
UCP2 | TERT578-592 | KSVWSKLQSIGIRQH | HLA-DR | ||
UCP3 1 | TERT916-930 | GTAFVQMPAHGLFPW | HLA-DR | ||
UCP4 | TERT1041-1055 | SLCYSILKAKNAGMS | HLA-DR | ||
p541 | TERT541-555 | LAKFLHWLMSVYVVE | HLA-DP4 | 2011 | [102,103] |
p573 | TERT573-587 | LFFYRKSVWSKLQSI | HLA-DP4 | ||
p613 2 | TERT613-627 | RPALLTSRLRFIPKP | HLA-DP4 | ||
p386 | TERT386-400 | YWQMRPLFLELLGNH | HLA-DP4 | 2011 | [104] |
p660 3 | TERT660-689 | ALFSVLNYERARRPGLLGASVLGLDDIHRA | HLA-DR | ||
p6633 | TERT663-677 | SVLNYERARRPGLLG | HLA-DR | ||
p673 3 | TERT673-687 | PGLLGASVLGLDDIH | HLA-DR | ||
GV1001 2 | TERT611–626 | EARPALLTSRLRFIPK | HLA-DP4 | 2006 | [101] |
p766 | TERT766-780 | LTDLQPYMRQFVAHL | HLA-DR | 2003 | [100] |
p6723 | TERT672-686 | RPGLLGASVLGLDDI | HLA-DR | 2002 | [99] |
Cancer type | Treatment | Responders | Overall Survival and anti-TERT CD4 T Cell Response at: | Ref. | ||
---|---|---|---|---|---|---|
Baseline | Post-Treatment | Baseline | Post-Treatment | |||
Metastatic non-small cell lung cancer (NSCLC) | Platinum-based chemo therapies | 38% (32/84) | ND | Patients with CD: median OS 53 months in TERT responders vs. 40 months in non-responders (p = 0.049) | - | [105] |
Non-small cell lung cancer (NSCLC) | Platinum-based chemo therapies | 45% (39/87) of localized 24% (20/83) of metastatic | ND | Two-year OS rate of 59% in anti-TERT Th1highvs. 22% in anti-TERT Th1low (p = 0.006). Similar significant differences in localized and metastatic disease analyzed separately | - | [110] |
Metastatic Renal cell carcinoma (mRCC) | Rapalog everolimus | 48% (11/23) | 74% (17/23) two months after treatment | ND | Better PFS achieved in patients with increased anti-TERT Th1 immunity and reduced Treg | [112] |
Metastatic anal squamous cell carcinoma | Docetaxel, cisplatin and fluorouracil (DCF) | 27% (17/64) | 32% (16/50) one month after the last DCF cycle | Median PFS p = 0.059) | One-year PFS rate of 62.5% in TERT responders vs. 23.5 % in non-responders, (p = 0.017) | [111] |
TERT MHC-II Based Therapy | Cancer | Phase | Estimated Enrollment | Status | ID |
---|---|---|---|---|---|
UCPVax: pool UCPs peptides | Metastatic NSCLC | I/II | 54 | Recruiting | NCT02818426 |
UCPVax -Glio: pool UCPs peptides | Glioblastoma | I/II | 28 | Recruiting | NCT04280848 |
Optim-UCPVax: pool UCPs + Nivolumab (anti-PD-1) | Advanced NSCLC | II | 111 | Not yet recruiting | NCT04263051 |
VolATIL: pool UCPs (UCPVax) + Atezolizumab (anti-PD-L1) | Squamous Cell Carcinoma Cervical cancer Advanced Anal Carcinoma | II | 47 | Not yet recruiting | NCT03946358 |
GV1001 + Gemcitabine + Capecitabine | Pancreatic cancer | III | 148 | Unknown | NCT02854072 |
INVAC-1: modified TERT DNA plasmid | Chronic Lymphocytic Leukemia | II | 90 | Recruiting | NCT03265717 |
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Dosset, M.; Castro, A.; Carter, H.; Zanetti, M. Telomerase and CD4 T Cell Immunity in Cancer. Cancers 2020, 12, 1687. https://doi.org/10.3390/cancers12061687
Dosset M, Castro A, Carter H, Zanetti M. Telomerase and CD4 T Cell Immunity in Cancer. Cancers. 2020; 12(6):1687. https://doi.org/10.3390/cancers12061687
Chicago/Turabian StyleDosset, Magalie, Andrea Castro, Hannah Carter, and Maurizio Zanetti. 2020. "Telomerase and CD4 T Cell Immunity in Cancer" Cancers 12, no. 6: 1687. https://doi.org/10.3390/cancers12061687