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Establishing the applicability of cancer vaccines in combination with chemotherapeutic entities: current aspect and achievable prospects

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  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Cancer immunotherapy is one of the recently developed cancer treatment modalities. When compared with conventional anticancer drug regimens, immunotherapy has shown significantly better outcomes in terms of quality of life and overall survival. It incorporates a wide range of immunomodulatory modalities that channel the effects of the immune system either by broadly modulating the host immune system or by accurately targeting distinct tumor antigens. One such treatment modality that has gained interest is cancer vaccine therapy which acts by developing antibodies against tumor cells. Cancer vaccines target individual peptides or groups of antigens that are released by tumor cells and presented by the APCs. This also initiates an effective process to activate the host immune responses. Studies on various types of cancer vaccines are conducted, out of which only few are approved by FDA for clinical uses. Despite of documented safety and efficacy of conventional chemotherapy and cancer vaccines, individually they did not produce substantial results in eradication of the cancer as a monotherapy. Hence, the combination approach holds the extensive potential to provide significant improvement in disease outcomes. Certain chemotherapy has immunomodulatory effects and is proven to synergize with cancer vaccines thereby enhancing their anti-tumor activities. Chemotherapeutic agents are known to have immunostimulatory mechanisms apart from its cytotoxic effect and intensify the anti-tumor activities of vaccines by various mechanisms. This review highlights various cancer vaccines, their mechanism, and how their activity gets affected by chemotherapeutic agents. It also aims at summarizing the evidence-based outcome of the combination approach of a cancer vaccine with chemotherapy and a brief on future aspects.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AEs:

: Adverse events

APCs:

: Antigen-presenting cells

ATP:

: Adenosine triphosphate

B7-H3:

: B7 Homolog 3

B7-H4:

: B7 Homolog 4

CBR:

: Clinical Benefit Rate

CD19:

: Cluster of Differentiation 19

CD30:

: Cluster of Differentiation 30

CD40:

: Cluster of differentiation 40

CD70:

: Cluster of Differentiation 70

CD8 + :

: Cluster of differentiation 8

CDKs:

: Cyclin-dependent kinases

CEA:

: Carcinoembryonic antigen

cGMP:

: Guanosine 3',5'-cyclic monophosphate

CRC:

: Colorectal cancer

CT83:

: Cancer/Testis Antigen 83

CTLA-4:

: Cytotoxic T lymphocyte associated protein 4

CY:

: Cyclophosphamide

DAMPs:

: Damage-associated molecular patterns

DCs:

: Dendritic cells

DFRS:

: Distant recurrence-free survival

DFS:

: Disease-free survival

DLTs:

: Dose-limiting toxicities

DNA:

: Deoxyribonucleic acid

EGFR:

: Epidermal growth factor receptor

GI:

: Gastrointestinal

GM-CSF:

: Granulocyte–macrophage colony-stimulating factor

GP100:

: Glycoprotein 100

HCV:

: Hepatitis C virus

HER2:

: Human epidermal growth factor 2

HLA:

: Human leukocyte antigen

HMGB1:

: High mobility group box 1 protein

HPV 16/17:

: Human papillomavirus 16/17

ICD:

: Immunologic cell death

iDFS:

: Invasive disease-free survival

IDO:

: Indoleamine-2,3-dioxygenase

IFN-α:

: Interferons-alpha

IFN-γ:

: Interferon‐gamma

IGF1R:

: Insulin-like growth factor 1 receptor

IMRT:

: Intensity-modulated radiotherapy

IR:

: Immunological response

LAG3:

: Lymphocyte Activation Gene 3

LCK:

: Lymphocyte-specific protein tyrosine kinase

LPA1:

: Lysophosphatidic acid

MAGEA1-40:

: Melanoma-associated antigen

MBC:

: Metastatic Breast Cancer

MDSCs:

: Myeloid-derived suppressor cells

mFOLFOX6:

: Combined chemotherapy including leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin

MHC-II:

: Major histocompatibility complex class II

MTD:

: Maximum tolerated dose

MUC1:

: Mucin 1

NCOA1:

: Nuclear receptor co-activator

NK cells:

: Natural killer cells

NYSEO 1:

: New York oesophageal squamous cell carcinoma

ORR:

: Objective response rate

OS:

: Overall survival

pCR:

: Pathological complete response

PCR:

: Polymerase chain reaction

PD1/PDL1:

: Programmed death ligand- 1

PEP-3:

: Epidermal growth factor receptor variant III (EGRRvIII)- specific peptide

PSA:

: Prostate stimulating antigen

PSA:

: Prostate-specific antigen

RFS:

: Recurrence-free survival

RLRs:

: RIG-I-like Receptors

SBRT:

: Stereotactic Body Radiation

SKILS:

: Skin-test infiltrating lymphocytes

SLP:

: Synthetic long peptide

Sp17:

: Sperm protein 17

STAT1:

: Signal transducer, and activator of transcription 1

STAT3:

: Signal transducer and activator of transcription 3

STINGs:

: Stimulator of Interferon Genes

TAA:

: Tumor-associated antigens

TC-1:

: T -cytotoxic 1

TCR:

: T-cell receptor

TCRA:

: T-cell receptor alpha

TCRD:

: T Cell Receptor Delta Locus

TCRG:

: T-cell Receptor Gamma

TGF-β:

: Transforming growth factor-β

TLRs:

: Toll-like Receptors

TME:

: Tumor microenvironment

TNBC:

: Triple-negative breast cancer

TNF:

: Tumor necrosis factor

Tregs:

: Regulatory T-cells

TRICOM:

: Three human T-cell costimulatory molecules

TTP:

: Time to progression

VSV:

: Vesicular stomatitis virus

WT-1:

: Wilms' tumor suppressor gene1

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Acknowledgements

The authors are grateful to Prof. Gaurang B. Shah, Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India for kind support and guidance in manuscript preparation. The authors also extend their appreciation to L. M. College of Pharmacy, Ahmedabad, India for providing continuous library resources support throughout literature survey and data collection.

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  1. Nirjari Kothari, Humzah Postwala, Aanshi Pandya, Aayushi Shah and Yesha Shah contributed equally.

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  1. Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, 380009, India

    Nirjari Kothari, Humzah Postwala, Aanshi Pandya, Aayushi Shah, Yesha Shah & Mehul R. Chorawala

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NK, HP, AP, AS, YS—Manuscript first draft preparation and subsequent editing, Literature and data survey, Figures and diagram conception and designing. MRC—Review topic conception, Design of content and skeleton, Manuscript draft review and editing; Figures and Tables conception, Designing and Editing.

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Kothari, N., Postwala, H., Pandya, A. et al. Establishing the applicability of cancer vaccines in combination with chemotherapeutic entities: current aspect and achievable prospects. Med Oncol 40, 135 (2023). https://doi.org/10.1007/s12032-023-02003-y

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