A Plant-Derived Antigen–Antibody Complex Induces Anti-Cancer Immune Responses by Forming a Large Quaternary Structure

Kim, Deuk-Su; Kang, Yejin; Lee, Kyung Jin; Lu, Qiao; Ko, Kinarm; Kim, Dae Heon; Myeung, Soon Chul; Ko, Kisung

doi:10.3390/ijms21165603

Cited by 5 publications

(13 citation statements)

References 51 publications

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“…The Fc fragment remarkably enhances the plasma half-life of their fused proteins or peptides through its FcRn interaction, eventually prolonging their therapeutic activities [43]. Additionally, the Fc fragment interacts with Fc receptors on immune cells to provoke antigen presentation, inducing immune responses [44,45]. Furthermore, regarding protein expression, the Fc-fused proteins in general exhibit better protein expression [29].…”

Section: Discussionmentioning

confidence: 99%

“…X57086) to construct the EpCAM-IgM Fc fusion protein, and this was cloned under the CaMV promoter in the plant expression vector pRCV2 to generate pRCV2 EpCAM-IgM Fc carrying the hygromycin phosphotransferase (hpt) gene for Chinese cabbage (B. rapa L. ssp. pekinensis) transformation [45]. The 30 amino acids (MATQRRANPSSLHLITVFSLLAAVVSAEVD) as an ER signal peptide from Nicotiana plumbaginifolia was fused to N-terminus of the cleavage site (Thr17-Ala23).…”

Section: Plant Expression Vector and Agrobacterium Strainmentioning

confidence: 99%

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Expression of Colorectal Cancer Antigenic Protein Fused to IgM Fc in Chinese Cabbage (Brassica rapa)

Lee

Lim

et al. 2020

Plants

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The epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen and a potential target for tumor vaccine. The EpCAM is a cell-surface glycoprotein highly expressed in colorectal carcinomas. The objective of the present study is to develop an edible vaccine system through Agrobacterium-mediated transformation in Chinese cabbage (Brassica rapa). For the transformation, two plant expression vectors containing genes encoding for the EpCAM recombinant protein along with the fragment crystallizable (Fc) region of immunoglobulin M (IgM) and Joining (J)-chain tagged with the KDEL endoplasmic reticulum retention motif (J-chain K) were constructed. The vectors were successfully transformed and expressed in the Chinese cabbage individually using Agrobacterium. The transgenic Chinese cabbages were screened using genomic polymerase chain reaction (PCR) in T0 transgenic plant lines generated from both transformants. Similarly, the immunoblot analysis revealed the expression of recombinant proteins in the transformants. Further, the T1 transgenic plants were generated by selfing the transgenic plants (T0) carrying EpCAM–IgM Fc and J-chain K proteins, respectively. Subsequently, the T1 plants generated from EpCAM–IgM Fc and J-chain K transformants were crossed to generate F1 plants carrying both transgenes. The presence of both transgenes was validated using PCR in the F1 plants. In addition, the expression of Chinese cabbage-derived EpCAM–IgM Fc × J-chain K was evaluated using immunoblot and ELISA analyses in the F1 plants. The outcomes of the present study can be utilized for the development of a potential anti-cancer vaccine candidate using Chinese cabbage.

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Section: Discussionmentioning

confidence: 99%

Section: Plant Expression Vector and Agrobacterium Strainmentioning

confidence: 99%

Expression of Colorectal Cancer Antigenic Protein Fused to IgM Fc in Chinese Cabbage (Brassica rapa)

Lee

Lim

et al. 2020

Plants

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“…The Ag:IgG IC vaccination also induces functional humoral antibody responses to tumor Ags. In a recent study by Kim et al [ 97 ], a recombinant Ag antibody IC was generated. Through the production of recombinant GA733, an epithelial cell adhesion molecule (EpCAM), Fc fusion protein, and an anti-GA733 mAb, anti-GA733 IgG ICs were obtained.…”

Section: Targeting Dcs For Cancer Vaccination Via Fcγrs: Mechanistic Principlesmentioning

confidence: 99%

“…IgG ICs can be highly variable [ 105 ], and a disadvantage of full-length Ag:IgG ICs [ 97 ] is their undefined size and valency, a factor to keep in mind especially in the case of polyclonal ICs. From a clinical point of view, this intrinsic heterogeneity and potential folding alterations may hamper the establishment of clear molecular modes of action (MoA), a requirement for rational drug design.…”

Section: The Long Way To the Clinic: Lessons Learned From Translational Modelsmentioning

confidence: 99%

Dendritic Cell Tumor Vaccination via Fc Gamma Receptor Targeting: Lessons Learned from Pre-Clinical and Translational Studies

2021

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Despite significant recent improvements in the field of immunotherapy, cancer remains a heavy burden on patients and healthcare systems. In recent years, immunotherapies have led to remarkable strides in treating certain cancers. However, despite the success of checkpoint inhibitors and the advent of cellular therapies, novel strategies need to be explored to (1) improve treatment in patients where these approaches fail and (2) make such treatments widely and financially accessible. Vaccines based on tumor antigens (Ag) have emerged as an innovative strategy with the potential to address these areas. Here, we review the fundamental aspects relevant for the development of cancer vaccines and the critical role of dendritic cells (DCs) in this process. We first offer a general overview of DC biology and routes of Ag presentation eliciting effective T cell-mediated immune responses. We then present new therapeutic avenues specifically targeting Fc gamma receptors (FcγR) as a means to deliver antigen selectively to DCs and its effects on T-cell activation. We present an overview of the mechanistic aspects of FcγR-mediated DC targeting, as well as potential tumor vaccination strategies based on preclinical and translational studies. In particular, we highlight recent developments in the field of recombinant immune complex-like large molecules and their potential for DC-mediated tumor vaccination in the clinic. These findings go beyond cancer research and may be of relevance for other disease areas that could benefit from FcγR-targeted antigen delivery, such as autoimmunity and infectious diseases.

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“…Moreover, unlike bacterial cells, plants have post-translational modification systems similar to those of mammalian cells, such as glycosylation. Since plant cells are eukaryotic and have an endomembrane system and secretory pathway ( Loh & Wayah, 2014 ), plants can produce and assemble correctly folded and complex mammalian proteins in their cells ( Menassa, Ahmad & Joensuu, 2012 ; Kim et al, 2020 (IJMS); Lee et al, 2020b (Plants)). Thus, plants are considered as an attractive alternative for the production of therapeutic recombinant proteins ( Lee & Ko, 2017 ; Nausch et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of leaf position and days post-infiltration on transient expression of colorectal cancer vaccine candidate proteins GA733-Fc and GA733-FcK in Nicotiana benthamiana plant

Kim

Kang

Park

et al. 2021

PeerJ

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Immunization with thetumor-associated antigen GA733 glycoprotein, which is highly expressed in colorectal cancer, is considered to be a promising strategy for cancer prevention and treatment. We cloned a fusion gene of GA733 and immunoglobulin Fc fragment (GA733-Fc), and that of GA733-Fc and an endoplasmic reticulum retention motif (GA733-FcK) into the Cowpea mosaic virus (CPMV)-based transient plant expression vector, pEAQ-HT. Agrobacterium tumefaciens (LBA4404) transformed with the vectors pEAQ-HT-GA733-Fc and pEAQ-HT-GA733-FcK was infiltrated into the leaves of Nicotiana benthamiana plants. To optimize harvesting of leaf to express therapeutic glycoproteins both spatially and temporally, protein expression levels at various leaf positions (top, middle, and base) and days post-infiltration (dpi) were investigated. The GA733-Fc and GA733-FcK genes were detected in leaves at 1–10 dpi using PCR. As assessed by western blot, GA733-Fc and GA733-FcK were expressed at the highest levels in the top leaf position at 5 dpi, and GA733-FcK was expressed more than GA733-Fc. The proteins were successfully purified from infiltrated N. benthamiana leaves using protein A affinity chromatography. ELISA verified that an anti-GA733 antibody recognized both purified proteins. Thus, a functional GA733-Fc colorectal cancer vaccine protein can be transiently expressed using a CPMV virus-based vector, with an optimized expression time and leaf position post-infiltration.

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A Plant-Derived Antigen–Antibody Complex Induces Anti-Cancer Immune Responses by Forming a Large Quaternary Structure

Cited by 5 publications

References 51 publications

Expression of Colorectal Cancer Antigenic Protein Fused to IgM Fc in Chinese Cabbage (Brassica rapa)

Expression of Colorectal Cancer Antigenic Protein Fused to IgM Fc in Chinese Cabbage (Brassica rapa)

Dendritic Cell Tumor Vaccination via Fc Gamma Receptor Targeting: Lessons Learned from Pre-Clinical and Translational Studies

Effect of leaf position and days post-infiltration on transient expression of colorectal cancer vaccine candidate proteins GA733-Fc and GA733-FcK in Nicotiana benthamiana plant

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