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Table 2 Preclinical studies of ICIs combine with nanotherapy

From: Strategies to enhance the therapeutic efficacy of anti-PD-1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody in cancer therapy

Author, year

Types of nanotherapy

Nanotherapeutic strategies

ICI

Mouse model

Immune cells

Anti-tumor efficacy

Zhang et al. 2022 [210]

Nanoparticle

Polylysine, ironoxide, and CpG + radiotherapy

Anti-CTLA-4 antibody

B78, MyC-CaP, TC11 tumor mouse models

M1 TAM

M2 TAM

CD4+ T cells

CD8+ T cells

1. The combination therapy inhibited tumor growth, enhanced adaptive anti-tumor immunity

Cao et al. 2021 [211]

Nanoparticle

CpG-decorated gold nanoparticles + radiotherapy

Anti-PD-1 antibody

GL261 tumor mouse model

M1 TAM

M2 TAM

CD4+ T cells

CD8+ T cells

1. The combination therapy inhibited distant tumor growth in mice

2. The combination therapy synergistically modulated TME

Guan et al. 2022 [199]

Nanoparticle

Radio-immunostimulant nanomedicine (IPI549@HMP)

Anti-PD-L1 antibody

Postsurgical CT26 tumor mouse model

M1 TAM

M2 TAM

MDSCs

CD8+ T cells

1. IPI549@HMP increased sensitivity to PD-L1 therapy

2. The combination therapy resulted in postoperative TME remodeling and inhibition of local residual and distant tumors

Dai et al. 2022 [212]

Nanoparticle

PDT + Poly

Anti-PD-L1 antibody

CT26, B16F10

tumor mouse model

M1 TAM

CD4+ T cells

CD8+ T cells

1. The combination therapy achieved nearly 100% ORR in the mouse model

2. High levels of chemokines and CD8+ T cells in TME enhanced the anti-tumor efficacy of ICI

Liu et al. 2019 [213]

Nanorings

Ferrimagnetic vortex-domain iron oxide nanorings

Anti-PD-L1 antibody

4T1 tumor mouse model

MDSCs

CD8+ T cells

1. The combination therapy increased CD8+ T cells infiltration and down-regulated MDSCs levels,

2. Eradicated primary 4T1 tumors without recurrence and inhibited distant metastasis

Nie et al. 2019 [201]

Magnetic nano-clusters

Magnetic nano-clusters armed with responsive PD-1 antibody

Anti-PD-1 antibody

Malignant 4T1 tumor mouse model

Tregs

CD8+ T cells

The combination therapy achieved inhibition of tumor growth with few side effects

Pham et al. 2021 [214]

Nanoparticle

Paclitaxel-loaded, PD-L1-targeted albumin nanoparticles

Anti-PD-L1 antibody

EMT-6 tumor mouse model

DCs

CD4+ T cells

CD8+ T cells Tregs

PD-L1/PTX@HSA had shown strong anti-tumor efficacy both in vivo and in vitro

Kuai et al. 2018 [34]

Nanodiscs

Nanodiscs deliver chemotherapy drugs

Anti-PD-1 antibody

CT26, MC38 tumor mouse model

CD8+ T cells

1. Delivery of doxorubicin via nanodiscs enhanced the anti-tumor immunoefficacy of ICI

2. The combination therapy induced complete tumor regression and prevented tumor recurrence in 80% to 88% of animals

Guo et al. 2022 [215]

Nanoparticle

GCT@CM NPs

Anti-PD-L1 antibody

B78 tumor mouse model

CD4+ T cells

CD8+ T cells Tregs

1. GCT@CM NPs induced tumor ICD

2. The combination therapy enhanced the infiltration of CD4+ T cells and CD8+ T cells, reduced the proportion of Tregs

3. The combination therapy inhibited tumor growth and induced effective immune response

Moon et al. 2022 [216]

Nanoparticle

PD-NPs

Anti-PD-L1 antibody

4T1 tumor mouse model

CD8+ T cells Tregs

PD-NPs could deliver anti-PD-L1 peptide and doxorubicin to the tumor site and inhibit tumor growth, showing significant anti-tumor effects

Li et al. 2022 [217]

Nanocomplex

MUSIC

Anti-PD-1 antibody

Luciferase expressing

4T1 (Luc-4T1) tumor mouse model

CD4+ T cells

CD8+ T cells

1. MUSIC enhanced the sensitivity of anti-PD-1 antibody

2. The combination therapy inhibited tumor growth in mice and induced immune memory to enhance anti-tumor response

Yu et al. 2022 [200]

Nanoreactor

Pt-PDA

Anti-PD-1 antibody

4T1 tumor mouse model

M1 TAM

M2 TAM

CD4+ T cells

CD8+ T cells Tregs

1. Pt-PDA enhanced the immune response against PD-1 antibody

2. The combination therapy improved the survival rate and induced immune memory in mice

Yu et al. 2022 [204]

Nanobody

PD-L1/TLR7 dual-targeting NDC

Anti-PD-1 antibody

CT26 tumor mouse model

CD8+ T cells

NK cells

PD-L1/TLR7 dual-targeting NDC is a promising strategy to enhance the efficacy of ICIs by enhancing innate and adaptive immunity to perform anti-tumor immunity

Choo et al. 2018 [205]

Nanovesicles

M1NVs

Anti-PD-L1 antibody

CT26 tumor mouse model

M1 TAM

M2 TAM

CD8+ T cells

1. M1NVs induced M2 TAM polarization into M1 TAM

2. The combination therapy inhibited tumor growth and alleviated drug resistance to anti-PD-L1 therapy

Li et al. 2020 [206]

Nanoparticle

Gadofullerene nanoparticles

Anti-PD-L1 antibody

4T1 tumor mouse model

M1 TAM

M2 TAM

CD8+ T cells

1. Gadofullerene nanoparticles induced M2 TAM polarization into M1 TAM and increased CD8+T cells infiltration

2. Gadofullerene nanoparticles showed synergistic anti-tumor effect with anti-PD-L1

Ni et al. 2020 [208]

Nanovaccine

BanNV

Anti-PD-1 antibody

MC38 tumor mouse model

DCs

CD4+ T cells

CD8+ T cells

1.BanNV was developed to enhance neoantigen immunogenicity and antigen presentation

2. The combination therapy anti-PD-1 therapy resulted in complete regression of 70% of tumors without recurrence

Kim et al. 2020 [209]

Nanovaccine

CpG adjuvant-embedded small lipid nanoparticles (OVAPEP-SLNP@CpG)

Anti-PD-1 antibody

E.G7 tumor mouse model

DCs CD8+ T cells

1. OVAPEP-SLNP@CpG enhanced antigen presentation, induced DCs maturation and CD8+T cell activation

2. The combination therapy had shown significant anti-tumor efficacy and prevented tumor recurrence

Wang et al. 2022 [218]

Nanomodulator

AuPtAg-mediated mild PTT + glucose oxidase

Anti-PD-L1 antibody

4T1 tumor mouse model

M1 TAM

M2 TAM

CD4+ T cells

CD8+ T cells

Tregs

1. The combination therapy induced M1 TAM polarization by mediating PTT

2. The combination therapy inhibited the growth of more than 90% of primary and distal tumors

Mamuti et al. 2022 [219]

Nano-agonist

Polyvalent peptide-based CD40 nano-agonist

Anti-PD-1 antibody

4T1, B16F10 tumor mouse model

DCs

CD4+ T cells

Tregs

1. The combination therapy increased CD8+T cells infiltration, delayed the early progression of tumor

2. The combination therapy Inhibited tumor growth and metastasis, and induced the body to produce a powerful immune response

  1. GCT@CM NPs: phosphorus dendrimer-copper complexes and toyocamycin loaded polymeric nanoparticles coated with cancer cell membranes; PD-NPs: anti-PD-L1 peptide-conjugated prodrug nanoparticles; MUSIC: microbubble-assisted ultrasound-guided immunotherapy of cancer; Pt-PDA: versatile photo-modulated nanoreactor; NDC: nanobody-drug conjugate; BanNV: bi-adjuvant neoantigen nanovaccine; OVAPEP-SLNP@CpG: CpG adjuvant-embedded small lipid nanoparticles