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Table 4. Examples of drugs targeting T cells
reg
Drug/Intervention Observation Ref.
Large molecules
CTLA-4 targeting agents Intra-tumoral T cells unchanged after ipilimumab or tremelimumab therapy Sharma et al. 2019 [138]
reg
In neo-adjuvant setting, ipilimumab transiently increased T cells
reg
In patients with metastatic melanoma, T cells are reduced after extended Retseck et al. 2018 [139]
reg
treatment time (> 3 months)
Bjoern et al. 2016 [104]
Patel et al. 2023 [140]
PD1 targeting agents Ratio of expression on T /T cells after immunotherapy potentially predicts Kumagai et al.
eff
reg
response 2020 [108]
+
PD1 T cells may be dysfunctional Lowther et al.
reg
2016 [141]
[142]
CCR-4 targeting agents Monoclonal antibody mogamulizumab (NCT02705105) showed limited activity Hong et al. 2022
(ORR or 10%) either as monotherapy or in combination with nivolumab
Blood and tumor T show a reduction for patients with ORR
reg
CCR-8 targeting agents Subpopulation of T cells express CCR-8 Kidani et al. 2022 [143]
reg
Blocking CCR-8 appears not to be associated with autoimmune adverse events in
animal studies Weaver et al.
[144]
Monoclonal antibody GS-1811 in early phase clinical trials (NCT05007782) 2022
CD25 targeting agents CD25 high-affinity subunit alpha Solomon et al.
[145]
Monoclonal antibody RO7296682 (RG6292) had no overt adverse events in 2020
animals
RO7296682 in clinical trials (NCT04158583)
[146]
IL-2 targeting agents Selective inhibition of trimeric and not dimeric CD25 leads to T cell reduction Wyant et al. 2023
reg
[147]
CEACAM-5 targeting agents CEACAM-5 and 6 is expressed on highly suppressive T cells Cole et al. 2023
reg
NEO201 reduces T cells
reg
Small molecules
Chemotherapies Low-dose cyclophosphamide and vaccines Le et al. 2012 [148]
Low-dose cyclophosphamide in CRC Ghiringhelli et al.
[149]
Docetaxel in NSCLC 2007
[150]
Sunitinib in RCC Scurr et al. 2017
Roselli et al. 2013 [151]
STAT3 (FOXP3) inhibition T cell reduction Revenko et al.
reg
2022 [152]
ATP-competitive PI3K-δ inhibitors Drug-related Grade 3/4 toxicities limiting continuous dosing and reducing Eschweiler et al.
[153]
potential efficacy 2022
T cell reduction in tumor tissue Tarantelli et al.
reg
Chemokines inducing T cells reduced in lymphoma patients 2021 [154]
reg
Non-ATP competitive PI3K-δ inhibitor Low grade 3/4 toxicity with no requirement of drug modifications Di Giacomo et al.
roginolisib (IOA-244) Safety in long-term treated uveal melanoma 2022 [110]
+
Reduction in T cells, increase in CD8 T and NK cells
reg
JAK1/2 inhibitors Reduction in T cells in patients with PMF responding to ruxolitinib Massa et al. 2014 [130]
reg
CDK4/6 Reduction in T cells and increase in T cells, with a greater reduction in patients Scirocchi et al.
reg
eff
with responses to therapy 2022 [155]
BCL2 (e.g., Venetoclax) Reduction in peripheral T cells and enhancement of immune cells Kohlhapp et al.
reg
2021 [156]
T cells: T regulatory cells; CTLA-4: cytotoxic T lymphocyte antigen-4; CCR: C-C chemokine receptor; NSCLC: non-small cell lung cancer; RCC:
reg
renal cell carcinoma; STAT3: signal transducer and activator of transcription 3; FOXP3: forkhead box protein P3; PI3K-δ: phosphoinositide-3-
kinase delta; NK: natural killer; JAK: Janus kinase; PMF: primary myelofibrosis.
ipilimumab have contributed to a greater disease-free survival and revolutionized treatment for high-risk
melanoma patients .
[163]