MASL for Oral Cancer

Not currently recruiting at 3 trial locations

Overseen By Mahnaz Fatahzadeh

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rowan University

Must not be taking: Topical steroids

Disqualifiers: Cognitive impairments, Pregnant, Breastfeeding, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential new treatment for oral cancer using Maackia amurensis seed lectin (MASL). Researchers aim to determine if MASL can affect cells from oral cancers and precancerous lesions, which are abnormal patches in the mouth. The trial will compare a lozenge containing MASL to a placebo lozenge without the active ingredient. This study targets individuals diagnosed with or suspecting oral cancer or precancerous lesions, such as white or red spots in the mouth. As an Early Phase 1 trial, this research focuses on understanding how MASL works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used a topical steroid product within the last 2 weeks.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it does mention that you should not have used a topical steroid product in the last 2 weeks.

Is there any evidence suggesting that MASL is likely to be safe for humans?

Research has shown that Maackia amurensis seed lectin (MASL) is safe for humans. In earlier studies, participants who took MASL experienced no adverse side effects, suggesting it is well-tolerated. While these results are encouraging, the current trials remain in the early stages. Researchers are primarily focused on ensuring safety and gathering initial data. So far, MASL appears to be a promising option without negative side effects for those who have tried it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for oral cancer, which often involve surgery, radiation, and chemotherapy, MASL uses a lozenge containing a unique active ingredient. MASL is derived from mistletoe, and researchers are hopeful because it may offer a gentler approach by targeting cancer cells directly without the harsh side effects of traditional therapies. This new delivery method, using a lozenge, could potentially provide patients with a more convenient and less invasive treatment option.

What evidence suggests that MASL might be an effective treatment for oral cancer?

Research suggests that a substance from the Maackia amurensis plant, called MASL, might help treat oral squamous cell carcinoma (OSCC). Studies have found that MASL can slow the growth and spread of these cancer cells by interfering with certain processes that cancer cells need to grow. Early results also indicate that MASL might help the body attack cancer cells by lowering levels of certain proteins, like podoplanin (PDPN), often present in these tumors. In this trial, participants will receive either a lozenge containing MASL or a placebo lozenge without MASL. Although the effects in real patients are still under study, these findings show promising potential for MASL as a treatment. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with white or red spots/lesions in the mouth, diagnosed as oral cancer or precancer. It's open to smokers and non-smokers who are generally healthy, have good organ function, and no severe illnesses. Pregnant women, breastfeeding mothers, those unable to consent, on steroids recently or with hearing/language issues can't join.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I am scheduled for a biopsy or surgery as part of my treatment plan.

Both smokers and non-smokers can participate.

Exclusion Criteria

I have used a topical steroid in the last 2 weeks.

You have difficulty hearing or communicating verbally.

Abstinence or use of adequate contraception will be required for women of childbearing potential and men of reproductive potential.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Evaluation

Measure morphology and podoplanin (PDPN) expression by immunohistochemistry of cells included in initial biopsies of oral lesions

1 day to 4 weeks

Treatment

Patients receive lozenges containing MASL or placebo to evaluate the effect on PDPN expression and morphology of OSCC cells

4 weeks

Follow-up

Participants are monitored for changes in PDPN expression and morphology of OSCC cells post-treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MASL

Trial Overview The study tests MASL's effectiveness against oral cancer by comparing it to a placebo. Participants will be randomly assigned to receive either MASL or an inactive substance without knowing which one they're getting.

How Is the Trial Designed?

Group I: MASL treated Experimental Treatment 1 Intervention

Patients treated with lozenge containing MASL

Group II: Placebo treated Placebo Group 1 Intervention

Patients treated with lozenge without MASL

Who Is Running the Clinical Trial?

Rowan University

Lead Sponsor

Trials

25

Recruited

3,000+

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

Published Research Related to This Trial

Maackia amurensis agglutinin shows strong reactivity with non-small cell lung cancer (NSCLC) cells and tissue samples, indicating its potential as a diagnostic tool for NSCLC.

This lectin not only identifies NSCLC cells but also induces apoptosis in these cells through a specific mechanism involving the regulation of apoptosis-related proteins, suggesting its potential as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential importance of Maackia amurensis agglutinin in non-small cell lung cancer. Mehta, S., Chhetra, R., Srinivasan, R., et al.[2016]

MAL-II, a lectin from Amur seeds, demonstrated significant antitumor activity against human anaplastic thyroid cancer cells (8505C) by altering the expression of various cancer-related and anticancer genes, as shown through RNA-Seq analysis.

The treatment with MAL-II led to the downregulation of several cancer-promoting genes and the upregulation of anticancer genes, indicating its potential as a therapeutic candidate by affecting key signaling pathways like Ras, p53, and apoptosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RNA-Seq transcriptome analysis reveals Maackia amurensis leukoagglutinin has antitumor activity in human anaplastic thyroid cancer cells. Bektas, S., Kaptan, E.[2022]

Abrus agglutinin (AGG) effectively inhibits epithelial-to-mesenchymal transition (EMT) in oral cancer cells by activating p73, which suppresses the expression of Snail, a key protein involved in cancer progression.

AGG not only reduces the invasiveness and stemness of oral cancer cells but also alters the expression of critical proteins, leading to decreased Snail and increased E-cadherin levels in treated tumor samples, indicating its potential as a therapeutic agent against oral cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

p73 induction by Abrus agglutinin facilitates Snail ubiquitination to inhibit epithelial to mesenchymal transition in oral cancer. Sinha, N., Meher, BR., Naik, PP., et al.[2020]

WSMoL, a water-soluble lectin from Moringa oleifera, demonstrated significant antitumor activity in mice with sarcoma 180 tumors, particularly at safe doses of 5 and 10 mg/kg, leading to reduced tumor weight and cell dissemination.

At a higher dose of 200 mg/kg, WSMoL showed acute toxicity with 60% mortality, but at 100 mg/kg, it was safe with no deaths and no significant changes in blood parameters, indicating a need for careful dosing in therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and antitumor activity of the water-soluble lectin from Moringa oleifera Lam. Seeds (WSMoL) in sarcoma 180-bearing mice. Brito, JS., Marinho, AO., Coelho, LCBB., et al.[2023]

A monoclonal antibody (NZ-1) and a lectin (MASL) targeting the PDPN receptor effectively inhibited the migration of oral squamous cell carcinoma (OSCC) cells at low concentrations and reduced cell viability at higher concentrations, indicating their potential as therapeutic agents.

Both NZ-1 and MASL induced cell death through a unique mechanism involving mitochondrial membrane permeability transition, leading to nonapoptotic necrosis, and MASL was particularly effective in reducing OSCC spread in zebrafish models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms. Ochoa-Alvarez, JA., Krishnan, H., Pastorino, JG., et al.[2022]

Machilin D (Mach), a compound isolated from Saururus chinensis, exhibits significant cytotoxic effects against oral squamous cell carcinoma (OSCC) cells, indicating its potential as a therapeutic agent for this aggressive cancer.

The mechanism of action for Mach involves promoting apoptosis and autophagy while inhibiting necroptosis, primarily through the suppression of key signaling pathways like FAK/Src and PI3K/AKT/mTOR, which are crucial for cancer cell survival and proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells. Yun, HM., Kwon, YJ., Kim, E., et al.[2023]

A lectin from Maackia amurensis (MASL) effectively targets the podoplanin (PDPN) receptor, which is involved in promoting tumor cell motility and metastasis, inhibiting cancer cell growth at very low concentrations (nanomolar levels).

This lectin remains biologically active after passing through the digestive system, allowing it to enter the bloodstream and inhibit melanoma cell growth and migration, suggesting its potential as a dietary agent in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration. Ochoa-Alvarez, JA., Krishnan, H., Shen, Y., et al.[2021]

In a study involving rats on total parenteral nutrition, both concanavalin-A and epidermal growth factor significantly increased cell proliferation in the small intestine and colon, indicating their potential as growth-promoting agents.

While concanavalin-A did not affect crypt branching, it worked synergistically with epidermal growth factor in the mid small intestine, suggesting that concanavalin-A could enhance intestinal function in vivo, contrary to its inhibitory effects observed in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of concanavalin-A and epidermal growth factor on epithelial cell proliferation in the rat intestine. Fitzgerald, AJ., Jordinson, M., Rhodes, JM., et al.[2019]

The study identified the N-linked glycan structure of Maackia amurensis leukoagglutinin (MAL), revealing eight glycans that are crucial for its lectin activities, particularly in binding to sialoglycoproteins.

Removal of high-mannose-type glycans from MAL significantly reduced its ability to agglutinate cells and detect human breast cancer MCF-7 cells, indicating that these glycans are essential for its functional efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of selective cleavage of high-mannose-type glycans of Maackia amurensis leukoagglutinin on sialic acid-binding activity. Kim, BS., Hwang, HS., Park, H., et al.[2016]

The study identified and sequenced cDNA clones for leukoagglutinin (MAL) from Maackia amurensis, revealing it has a high similarity (86.2% identity) to Maackia amurensis hemagglutinin (MAH).

Key amino acid substitutions in MAL and MAH were found to be critical for binding to sialic acid residues, as mutations at specific positions resulted in loss of binding ability, highlighting the importance of these residues in the lectins' function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sialic acid-binding motif of Maackia amurensis lectins. Yamamoto, K., Konami, Y., Irimura, T.[2019]

Maackia amurensis seed lectin (MASL) has been shown to significantly inhibit the growth and movement of oral squamous cell carcinoma (OSCC) cells by affecting the expression of about 27% of genes related to key signaling pathways, including TGFβ-SMAD and JAK-STAT.

MASL not only decreased the expression of important cancer-related genes like PDPN and SMAD5 but also inhibited critical signaling activities, suggesting its potential as a novel treatment for oral cancer, especially when used in combination with standard chemotherapy agents like doxorubicin and 5-fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways. Hamilton, KL., Sheehan, SA., Retzbach, EP., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12274232/

Effects of Maackia amurensis seed lectin (MASL) on OSCC ... These results suggest that protocols using MASL and photoimmunotherapies that target PDPN can be developed to effectively treat OSCC lesions in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006291X24004170

Maackia amurensis seed lectin (MASL) and soluble human ... Results from this study also confirm that MASL also can inhibit human oral squamous cell carcinoma (OSCC) cell growth and motility as previously reported ...

3. cureus.com cureus.com/articles/296328-the-promising-role-of-plant-derived-lectins-in-oral-cancer-therapeutics-a-systematic-review

The Promising Role of Plant-Derived Lectins in Oral ... Plant lectins suppress cancer cells by inducing apoptosis and/or autophagy by modulating various signalling pathways such as the caspase family, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33205348/

Effects of Maackia amurensis seed lectin (MASL) on oral ... Results from this study indicate that MASL decreases activity of JAK-STAT, TGFβ-SMAD, and Wnt-βCTN signaling pathways to inhibit OSCC growth and motility.

5. researchgate.net researchgate.net/publication/393798670_Effects_of_Maackia_amurensis_seed_lectin_MASL_on_OSCC_cell_morphology_PDPN_expression_growth_and_motility_in_a_phase_1_clinical_trial

(PDF) Effects of Maackia amurensis seed lectin (MASL) on ... However, the effects of MASL on OSCC cells in oral cancer patients has not yet been reported. Methods We conducted a Phase 1 human clinical ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0021925825003151

Maackia amurensis seed lectin structure and sequence ... Indeed, MASL is being evaluated as a potential agent to inhibit oral cancer progression in an ongoing phase 1 clinical trial (NCT04188665 ). In spite of ...

7. plantmedia.com plantmedia.com/products/maackia-amurensis-amur-maackia-lectin-maa-mal-i-pure

Maackia amurensis Lectin (MAA/MAL I) - Pure - PlantMedia It has been exhibited that MAA inhibits oral squamous cell carcinoma growth and motility by decreasing activity of the JAK-STAT, TGFβ-SMAD, and Wnt-βCTN ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7855468/

Effects of Maackia amurensis seed lectin (MASL) on oral ... Results from this study indicate that MASL decreases activity of JAK-STAT, TGFβ-SMAD, and Wnt-βCTN signaling pathways to inhibit OSCC growth and motility.

9. synapse.patsnap.com synapse.patsnap.com/drug/ef35b38f5a6b4cc887c582d5de0afb47

Maackia amurensis seed lectin - Drug Targets, Indications, ... RESULTS: MASL administration was found to be safe and did not produce any adverse effects in any patients. While this single dose did not affect OSCC cell ...