Immunization with placenta-specific 1 (plac1) induces potent anti-tumor responses and prolongs survival in a mouse model of melanoma

Rahdan, Shaghayegh; Razavi, Seyed Alireza; Shojaeian, Sorour; Shokri, Fazel; Amiri, Mohammad Mehdi; Zarnani, Amir Hassan

doi:10.1016/j.advms.2022.08.002

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…This could explain why therapeutic effect of anti-PLAC1 ADC was much greater than expected. We have recently showed immunoenhancement effect of intracellular plac1 in a mouse model of melanoma [39]. Similarly, and despite expression of PLAC1 in only 30% of MDA-MB-231 cells, we showed here that the size of the tumor in the anti-PLAC1 ADC-treated mice is at least 5 times smaller than that in the control group.…”

Section: Discussionsupporting

confidence: 73%

“…However, nude mice lack T cell immune responses and therefore the immunoenhancement potential of intracellular PLAC1 might not be the case in nude mice. In our previous study [39], we observed substantial proportion of tumor cells arising from B16F10 cells, which normally express plac1 in 10% of cell population. This nding implies that PLAC1 expression might be under control of tumor microenvironment and signaling from tumor-associated cells and extracellular matrix could enhance PLAC1 expression.…”

Section: Discussionmentioning

confidence: 76%

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Targeted therapy of breast cancer using PLAC1 antibody-drug conjugate

Mahmoudian,

Ghods,

Jeddi-Tehrani

et al. 2023

Preprint

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Background Placenta-specific 1 (PLAC1) is one of the oncoplacental genes ectopically expressed in a wide variety of cancers. Antibody drug conjugates (ADC) have the potential to substantially improve efficacy and reduce toxicity of treatment compared with cytotoxic small-molecule drugs and are recently being employed for treatment of cancers. Here, efficacy of a SN38-conjugated monoclonal anti-PLAC1 antibody was examined in breast cancer. Methods and Results Anti-human PLAC1 monoclonal antibodies were produced and characterized. SN38 was conjugated to an anti-PLAC1 antibody (clone: 2H12C12) and conjugation efficacy was evaluated by UV spectrophotometry. Post-conjugation reactivity was then tested using ELISA and flow cytometry. In vitro cytotoxicity profiling of 2H12C12-SN38 was examined on MDA-MB-231 breast cancer cells using a flourimetric assay. The effect of 2H12C12-SN38 on MDA-MB-231 tumor growth and angiogenesis ex vivo was tested by chorioallantoic membrane (CAM) assay followed by immunohistochemical analysis of tumor. Pharmacokinetics of 2H12C12-SN38 in mice was measured by successive venipuncture after ADC administration. Inhibitory effects of anti-PLAC1 ADC on tumor growth was assessed in nude mice xenograft model of human breast cancer. Anti-PLAC1 ADC exerted a substantial cytotoxicity on MDA-MB-231 cells starting from a concentration of about 33 nM. ADC also significantly decreased the growth of MDA-MB-231 tumors on CAM assay but did not show a significant effect on tumor angiogenesis. Pharmacokinetics of anti-PLAC1 ADC in mice showed an average half-life (t1/2) of about 80 hours. Treatment of nude mice with ADC resulted in a significant decrease in tumor size compared to isotype-matched antibody-SN38 conjugate, unconjugated anti-PLAC1 antibody or free SN38. Conclusion This is the first therapeutic application of anti-PLAC1 ADC in a xenograft model of human breast cancer. Our results reinforce on embryonic origin of cancers and shed light on the potential therapeutic benefits of targeting oncofetal antigens in human breast cancer.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 76%

Targeted therapy of breast cancer using PLAC1 antibody-drug conjugate

Mahmoudian,

Ghods,

Jeddi-Tehrani

et al. 2023

Preprint

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“…Immune escape and tumor suppressor cells in the tumor microenvironment are important reasons for the hindered immune response [73][74][75]. Tumor cells and their surrounding cells and molecules work together in the tumor microenvironment to form a pattern of immune escape [76].…”

Section: Immune Escape and Tumor Suppressor Cellsmentioning

confidence: 99%

A Mannose-Modified Lipid Calcium Phosphate Nanoparticle Vaccine Increased the Anti-Tumor Immune Response by Modulating the Tumor Microenvironment

Wu,

Qian,

et al. 2024

Preprint

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With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

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“…Based on the aforementioned similarities between carcinogenesis and placentation, it could be inferred that the placenta can be considered a physiological tumor (125). In this context, the expression of placenta-specific antigens in different types of cancers has motivated many researchers to target them for cancer therapy (153)(154)(155)(156)(157)(158). Moreover, biological products derived from the placenta can remarkably hinder the growth, proliferation, and progression of cancers (159, 160).…”

Section: The Story Of the Link Between Placenta Development And Carci...mentioning

confidence: 99%

Placenta: an old organ with new functions

Khorami-Sarvestani,

Vanaki,

Shojaeian

et al. 2024

Front. Immunol.

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The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide nutrients, gases, and hormones to the developing fetus. The placenta has endocrine functions, orchestrates maternal adaptations to pregnancy at different periods of pregnancy, and acts as a selective barrier to minimize exposure of developing fetus to xenobiotics, pathogens, and parasites. Despite the fact that this ancient organ is central for establishment of a normal pregnancy in eutherians, the placenta remains one of the least studied organs. The first step of pregnancy, embryo implantation, is finely regulated by the trophoectoderm, the precursor of all trophoblast cells. There is a bidirectional communication between placenta and endometrium leading to decidualization, a critical step for maintenance of pregnancy. There are three-direction interactions between the placenta, maternal immune cells, and the endometrium for adaptation of endometrial immune system to the allogeneic fetus. While 65% of all systemically expressed human proteins have been found in the placenta tissues, it expresses numerous placenta-specific proteins, whose expression are dramatically changed in gestational diseases and could serve as biomarkers for early detection of gestational diseases. Surprisingly, placentation and carcinogenesis exhibit numerous shared features in metabolism and cell behavior, proteins and molecular signatures, signaling pathways, and tissue microenvironment, which proposes the concept of “cancer as ectopic trophoblastic cells”. By extensive researches in this novel field, a handful of cancer biomarkers has been discovered. This review paper, which has been inspired in part by our extensive experiences during the past couple of years, highlights new aspects of placental functions with emphasis on its immunomodulatory role in establishment of a successful pregnancy and on a potential link between placentation and carcinogenesis.

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Immunization with placenta-specific 1 (plac1) induces potent anti-tumor responses and prolongs survival in a mouse model of melanoma

Cited by 8 publications

References 23 publications

Targeted therapy of breast cancer using PLAC1 antibody-drug conjugate

Targeted therapy of breast cancer using PLAC1 antibody-drug conjugate

A Mannose-Modified Lipid Calcium Phosphate Nanoparticle Vaccine Increased the Anti-Tumor Immune Response by Modulating the Tumor Microenvironment

Placenta: an old organ with new functions

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