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Journal of Cellular and Molecular... Feb 2022Immunotherapy is an attractive approach for treating cancer. T-cell engagers (TCEs) are a type of immunotherapy that are highly efficacious; however, they are challenged...
Immunotherapy is an attractive approach for treating cancer. T-cell engagers (TCEs) are a type of immunotherapy that are highly efficacious; however, they are challenged by weak T-cell activation and short persistence. Therefore, alternative solutions to induce greater activation and persistence of T cells during TCE immunotherapy is needed. Methods to activate T cells include the use of lectins, such as phytohemagglutinin (PHA). PHA has not been used to activate T cells in vivo, for immunotherapy, due to its biological instability and toxicity. An approach to overcome the limitations of PHA while also preserving its function is needed. In this study, we report a liposomal PHA which increased PHA stability, reduced toxicity and performed as an immunotherapeutic that is able to activate T cells for the use in future cancer immunotherapies to circumvent current obstacles in immunosuppression and T-cell exhaustion.
Topics: Humans; Immunotherapy; Lymphocyte Activation; Neoplasms; Phytohemagglutinins; T-Lymphocytes
PubMed: 35014164
DOI: 10.1111/jcmm.16885 -
Biochimica Et Biophysica Acta Mar 1981The subunit compositions of individual phytohemagglutinin isolectins from red kidney bean Phaseolus vulgaris were examined by isoelectric focusing and sodium dodecyl...
The subunit compositions of individual phytohemagglutinin isolectins from red kidney bean Phaseolus vulgaris were examined by isoelectric focusing and sodium dodecyl sulfate electrophoresis on polyacrylamide gels. Isoelectric focusing reveals heterogeneous but unique and non-overlapping protein band patterns for each of the homotetrameric isolectins, E4 and L4. Isoelectric focusing of the intermediate isolectins which contain both subunits (E3L1, E2L2, and E1L3) show all the protein bands common to isolectins E4 or L4 in proportions relative to their suggested subunit compositions. Polyacrylamide gel electrophoresis in a continuous sodium dodecyl sulfate buffer system gives a single protein band for all of the isolectins. In contrast, a discontinuous sodium dodecyl sulfate buffer procedure resolves isolectins E4 and L4 into single major protein bands of apparent molecular weights 31 700 (+/-600) and 29 900 (+/-200), respectively. Each of the intermediate isolectins contained both protein bands and their relative proportion, as determined by absorbance scanning, confirms the phytohemagglutinin isolectin subunit compositions as E4, E3L1, E2L2, E1L3, and L4.
Topics: Electrophoresis, Polyacrylamide Gel; Isoelectric Focusing; Lectins; Molecular Weight; Phytohemagglutinins; Protein Conformation
PubMed: 7236703
DOI: 10.1016/0005-2795(81)90156-2 -
Molecular Biotherapy Mar 1990Phytohemagglutinin retains the properties of a theoretically ideal biologic response modifier in that it is available in a purely mitogenic L4 isolectin form that is... (Review)
Review
Phytohemagglutinin retains the properties of a theoretically ideal biologic response modifier in that it is available in a purely mitogenic L4 isolectin form that is stable; previously studied extensively; applicable as a simple skin test to assess immune competence and guide therapy; broadly immunostimulating with respect to both activation and proliferation of effector cell pathways; amenable to targeting maneuvers; stimulative of endogenous cytokine production; conveniently administrable by multiple routes; applicable to both active and adoptive immunotherapies; rapidly interacting irreversibly with lymphocytes; readily applied as a vaccine adjuvant; apparently nonsensitizing; relatively nontoxic, with maximum effective levels well below those for major toxicity; free from stress induction; nononcogenic; noninfectious; related to other mitogenic lectins that have augmenting therapeutic potential; compatible with other therapeutic modalities and conductive to collaborative use of other BRMs; well-suited to application as a surgical adjuvant and for prophylaxis against malignancies or infections in susceptible individuals; applicative to debilitated, immunosuppressed, and myelosuppressed patients; probably compatible with pregnancy; and potentially cost-effective.
Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Drug Hypersensitivity; Fabaceae; Humans; Immunity, Cellular; Immunization, Passive; Immunologic Factors; Immunologic Techniques; Lectins; Lymphocyte Activation; Lymphocytes; Phytohemagglutinins; Plant Lectins; Plants, Medicinal
PubMed: 2185793
DOI: No ID Found -
International Immunopharmacology Jul 2023Leukocyte phytohemagglutinin (PHA-L) is a tetrameric isomer of phytohemagglutinin (PHA) purified from the red kidney bean (Phaseolus vulgaris) and is a well-known human...
Recombinant Phaseolus vulgaris phytohemagglutinin L-form expressed in the Bacillus brevis exerts in vitro and in vivo anti-tumor activity through potentiation of apoptosis and immunomodulation.
Leukocyte phytohemagglutinin (PHA-L) is a tetrameric isomer of phytohemagglutinin (PHA) purified from the red kidney bean (Phaseolus vulgaris) and is a well-known human lymphocyte mitogen. Due to its antitumor and immunomodulatory effects, PHA-L may serve as a potential antineoplastic agent in future cancer therapeutics. However, various negative consequences of PHA have been reported in the literature as a result of the restricted acquisition methods, including oral toxicity, hemagglutinating activity, and immunogenicity. There is a critical need to explore a new method to obtain PHA-L with high purity, high activity and low toxicity. In this report active recombinant PHA-L protein was successfully prepared by Bacillus brevius expression system, and the antitumor and immunomodulatory activities of recombinant PHA-L were characterized by in vitro and in vivo experiments. The results showed that recombinant PHA-L protein had stronger antitumor effect, and its anti-tumor mechanism was realized through direct cytotoxicity and immune regulation. Importantly, compared with natural PHA-L, the recombinant PHA-L protein showed the lower erythrocyte agglutination toxicity in vitro and immunogenicity in mice. Altogether, our study provides a new strategy and important experimental basis for the development of drugs with dual effects of immune regulation and direct antitumor activity.
Topics: Humans; Animals; Mice; Phytohemagglutinins; Phaseolus; Bacillus; Recombinant Proteins; Neoplasms; Apoptosis
PubMed: 37269742
DOI: 10.1016/j.intimp.2023.110322 -
Journal of Natural Medicines Mar 2024Chemotherapy is still a prevalent strategy for clinical lung cancer treatment. However, the inevitable emerged drug resistance has become a great hurdle to therapeutic...
Chemotherapy is still a prevalent strategy for clinical lung cancer treatment. However, the inevitable emerged drug resistance has become a great hurdle to therapeutic effect. Studies have demonstrated that the primary cause of drug resistance is a decrease in the chemotherapeutic medicine concentration. Several lectins have been confirmed to be effective as chemotherapy adjuvants, enhancing the anti-tumor effects of chemotherapy drugs. Here, we combined phytohemagglutinin (PHA), which has been reported possess anti-tumor effects, with chemotherapy drugs Cisplatin (DDP) and Adriamycin (ADM) on lung cancer cells to detect the sensitivities of PHA as a chemotherapy adjuvant. Our results demonstrated that the PHA significantly enhanced the sensitivity of lung cancer cells to DDP and ADM, and Western blot showed that PHA combined with DDP or ADM enhance cytotoxic effects by inhibiting autophagy and promoting apoptosis. More importantly, we found PHA enhanced the chemotherapeutic drugs cytotoxicity by changing the cell membrane to increase the intracellular chemotherapeutic drugs concentration. Besides, the combination of PHA and ADM increased the ADM concentration in the multidrug-resistant strain A549-R cells and achieved the drug sensitization effect. Our results suggest that PHA combined with chemotherapy can be applied in the treatment of lung cancer cells and lung cancer multidrug-resistant strains, and provide a novel strategy for clinical tumor chemotherapy and a new idea to solve the problem of drug resistance in clinical lung cancer.
Topics: Humans; Lung Neoplasms; Phytohemagglutinins; Phaseolus; Cell Membrane Permeability; Drug Resistance, Neoplasm; Cell Line, Tumor; Antineoplastic Agents; Doxorubicin; Apoptosis; Cell Proliferation
PubMed: 38265611
DOI: 10.1007/s11418-023-01772-0 -
Molecular Biotherapy Dec 1990Assuming that the attributes of the mitogenic-leukoaggglutinating (L4) isolectin of phytohemagglutinin as a proposed ideal biologic response modifier can be confirmed,... (Review)
Review
Assuming that the attributes of the mitogenic-leukoaggglutinating (L4) isolectin of phytohemagglutinin as a proposed ideal biologic response modifier can be confirmed, it could prove to be a highly versatile agent with broad therapeutic potential for several areas of management including cancer and cancer surgery adjuvant, critical infections (including that with the human immunodeficiency viruses), vaccine adjuvant, allograft transplantations, aplastic anemias, and extensive burns. The isolectin is predictably more likely to be effective as an adjuvant or adjunctive agent than as an induction agent. Initial evaluation in dogs would serve the double purpose of establishing a presumptive key role in veterinary medicine and expediting the development of its use in humans.
Topics: Animals; HIV Infections; Humans; Immunologic Factors; Neoplasms; Phytohemagglutinins
PubMed: 2288718
DOI: No ID Found -
Molecular Biotherapy Jun 1990Evidence is presented that suggests that PHA-L4 may exert the therapeutic effects of a theoretical ideal biological response modifier through its ability to do the... (Review)
Review
Evidence is presented that suggests that PHA-L4 may exert the therapeutic effects of a theoretical ideal biological response modifier through its ability to do the following: to assist remission induction in certain malignancies, to exhibit direct antitumor cytotoxic effects, to enhance antineoplastic effect of radiation and chemotherapy, to decrease the liability to malignant transformation, to promote differentiation and restore normal growth responses in neoplastic cells, to manifest minimal liability to suppressor activity that would inhibit tumor rejection or antitumor cytotoxicity, to repress graft rejection and graft-versus-host responses and amplify the immunosuppressive effects of other agents in allograft transplantations, to display a direct protective effect against damage from radiation and chemotherapy, to stimulate normal myelopoiesis, to reinforce responses against various infections, to amplify tumor immunogenicity, and to attract mononuclear cells to sites of injection or local application.
Topics: Adjuvants, Immunologic; Anemia, Aplastic; Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Humans; Immunologic Factors; Immunosuppressive Agents; Infections; Killer Cells, Natural; Lymphocyte Activation; Phytohemagglutinins; Radiation-Protective Agents
PubMed: 2194501
DOI: No ID Found -
Thoracic Cancer Jun 2021Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict...
T-cell response to phytohemagglutinin in the interferon-γ release assay as a potential biomarker for the response to immune checkpoint inhibitors in patients with non-small cell lung cancer.
BACKGROUND
Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict treatment response. Immune checkpoint inhibitors enhance the antitumor T-cell response, and interferon-γ plays an important role in this process. Therefore, this study evaluated whether the number of interferon-γ-releasing peripheral T cells after phytohemagglutinin stimulation in the interferon-γ release assay might act as a biomarker for the response of non-small cell lung cancer to immune checkpoint inhibitor treatment.
METHODS
Data were retrospectively collected regarding 74 patients with non-small cell lung cancer who had received immune checkpoint inhibitors. Pretreatment screening tests had been performed using the T-SPOT.TB assay, which quantifies the number of interferon-γ-releasing T cells (as immunospots) in response to phytohemagglutinin and tuberculosis-specific antigen stimulation. Clinical factors and the number of spots in the T-SPOT fields were evaluated for associations with patient outcomes. The median number of spots was used to categorize patients as having high or low values, and the two groups were compared.
RESULTS
Relative to patients with a low ratio, patients with a high ratio of phytohemagglutinin/tuberculosis-specific antigen spots (i.e. more responsive T cells) had significantly better progression-free survival after immune checkpoint inhibitor treatment. When we only considered patients with negative T-SPOT results, a high number of phytohemagglutinin-stimulated spots corresponded to significantly longer progression-free survival.
CONCLUSION
The T-SPOT.TB assay can be used to quantify the number of immunospots in response to antigen stimulation, which may predict the response to immune checkpoint inhibitors in patients with non-small cell lung cancer.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Non-Small-Cell Lung; Female; Humans; Immune Checkpoint Inhibitors; Interferon-gamma Release Tests; Lung Neoplasms; Male; Middle Aged; Phytohemagglutinins; Retrospective Studies; T-Lymphocytes
PubMed: 33943031
DOI: 10.1111/1759-7714.13978 -
Planta Medica Sep 1982
Review
Topics: Animals; Chemical Phenomena; Chemistry; Humans; Phytohemagglutinins; Plant Lectins; Plants
PubMed: 6755514
DOI: 10.1055/s-2007-970007 -
Molecular and Cellular Biochemistry Feb 2022Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an...
Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an exogenous pyrogen. When entering into the blood circulation, exogenous pyrogens principally interact with monocytes and macrophages and induce the release of pro-inflammatory cytokines. Monocytes and macrophages are the cells that fight against foreign invaders and acts as a primary line of immune defence. Similar to PHA, the chemical 2,4,6-trinitrophenol (TNP) also acts as an exogenous pyrogen. The study focused on the in vitro interaction of PHA and TNP with the human monocyte/macrophage cell model THP-1. The exposure and associated change in cellular morphology, organelle function, mechanism of cell death, inflammatory signalling and expression of inflammation-related genes were analyzed in different time periods. It was observed that PHA and TNP induce dose and time-dependent toxicity to monocytes/macrophages where the mechanism of cell death was different for PHA and TNP. Both PHA and TNP can evoke immune signalling with increased expression of inflammatory genes and associated activation of intracellular signalling cascades.
Topics: Humans; Inflammation; Monocytes; Phytohemagglutinins; Picrates; Signal Transduction; THP-1 Cells
PubMed: 34775567
DOI: 10.1007/s11010-021-04296-x