Recently, peptides that offer versatility in drug discovery for the successful treatment of cancers have emerged. Peptide-drug conjugates (PDCs) represent an important therapeutic strategy for increasing tumor penetration and selectivity. We previously reported that M, which is extracted from bee venom, targets M2 macrophages and improves tumor treatment in lung cancer. M is an amphipathic peptide with 26 amino acid residues (AIGAVLKVLTTGLPALISWIKRKRQQ) that specifically binds to M2-like TAMs. Mertansine (DM1) is a strong cytotoxic agent that interacts with tubulin and inhibits the assembly of tubulin into microtubules. Because it targets microtubules and inhibits cell cycle, its clinical efficacy as a potential anti-cancer agent has been studied. However, meaningful results have yet to be obtained in clinical trials, with patients also suffering several side effects, such as myelosuppression. Antibody drug conjugates (ADCs) are currently the most successful type of drug conjugates, consisting of antibody (targeting), linker (linking the antibody to the payload), and Payload (killing target cells). Payload is a cytotoxic compound and is divided into microtubule inhibitors, such as DM1, and DNA-damaging agents, such as anthracyclines. DM1 alone has not been developed as a drug but is currently used as an antibody-drug conjugate. It has been reported that the peptide LLC2B combined with DM1 exerts an anticancer effect in breast and esophageal squamous cell carcinoma, suggesting it could be developed as a potential PDC for tumor treatment. In the present study, we investigated the anti-cancer effects of M-DM1, which was synthesized using M as a carrier for targeting TAMs and DM1 as a payload. We found that M-DM1 exerts its therapeutic effects by specifically depleting M2-like TAMs in a melanoma mouse model. Through the regulation of M2-like TAMs, M-DM1 induced a significant increase in the infiltration of effector cells, such as CD8 T cells and natural killer (NK) cells, into the TME. Collectively, our results suggest that depleting M2-like TAMs in the TME by treatment with M-DM1 has immunotherapeutic effects in malignant melanoma.

Recently, peptides that offer versatility in drug discovery for the successful treatment of cancers have emerged. Peptide-drug conjugates (PDCs) represent an important therapeutic strategy for increasing tumor penetration and selectivity. We previously reported that M, which is extracted from bee venom, targets M2 macrophages and improves tumor treatment in lung cancer. M is an amphipathic peptide with 26 amino acid residues (AIGAVLKVLTTGLPALISWIKRKRQQ) that specifically binds to M2-like TAMs. Mertansine (DM1) is a strong cytotoxic agent that interacts with tubulin and inhibits the assembly of tubulin into microtubules. Because it targets microtubules and inhibits cell cycle, its clinical efficacy as a potential anti-cancer agent has been studied. However, meaningful results have yet to be obtained in clinical trials, with patients also suffering several side effects, such as myelosuppression. Antibody drug conjugates (ADCs) are currently the most successful type of drug conjugates, consisting of antibody (targeting), linker (linking the antibody to the payload), and Payload (killing target cells). Payload is a cytotoxic compound and is divided into microtubule inhibitors, such as DM1, and DNA-damaging agents, such as anthracyclines. DM1 alone has not been developed as a drug but is currently used as an antibody-drug conjugate. It has been reported that the peptide LLC2B combined with DM1 exerts an anticancer effect in breast and esophageal squamous cell carcinoma, suggesting it could be developed as a potential PDC for tumor treatment. In the present study, we investigated the anti-cancer effects of M-DM1, which was synthesized using M as a carrier for targeting TAMs and DM1 as a payload. We found that M-DM1 exerts its therapeutic effects by specifically depleting M2-like TAMs in a melanoma mouse model. Through the regulation of M2-like TAMs, M-DM1 induced a significant increase in the infiltration of effector cells, such as CD8 T cells and natural killer (NK) cells, into the TME. Collectively, our results suggest that depleting M2-like TAMs in the TME by treatment with M-DM1 has immunotherapeutic effects in malignant melanoma.

Recently, peptides that offer versatility in drug discovery for the successful treatment of cancers have emerged. Peptide-drug conjugates (PDCs) represent an important therapeutic strategy for increasing tumor penetration and selectivity. We previously reported that M, which is extracted from bee venom, targets M2 macrophages and improves tumor treatment in lung cancer. M is an amphipathic peptide with 26 amino acid residues (AIGAVLKVLTTGLPALISWIKRKRQQ) that specifically binds to M2-like TAMs. Mertansine (DM1) is a strong cytotoxic agent that interacts with tubulin and inhibits the assembly of tubulin into microtubules. Because it targets microtubules and inhibits cell cycle, its clinical efficacy as a potential anti-cancer agent has been studied. However, meaningful results have yet to be obtained in clinical trials, with patients also suffering several side effects, such as myelosuppression. Antibody drug conjugates (ADCs) are currently the most successful type of drug conjugates, consisting of antibody (targeting), linker (linking the antibody to the payload), and Payload (killing target cells). Payload is a cytotoxic compound and is divided into microtubule inhibitors, such as DM1, and DNA-damaging agents, such as anthracyclines. DM1 alone has not been developed as a drug but is currently used as an antibody-drug conjugate. It has been reported that the peptide LLC2B combined with DM1 exerts an anticancer effect in breast and esophageal squamous cell carcinoma, suggesting it could be developed as a potential PDC for tumor treatment. In the present study, we investigated the anti-cancer effects of M-DM1, which was synthesized using M as a carrier for targeting TAMs and DM1 as a payload. We found that M-DM1 exerts its therapeutic effects by specifically depleting M2-like TAMs in a melanoma mouse model. Through the regulation of M2-like TAMs, M-DM1 induced a significant increase in the infiltration of effector cells, such as CD8 T cells and natural killer (NK) cells, into the TME. Collectively, our results suggest that depleting M2-like TAMs in the TME by treatment with M-DM1 has immunotherapeutic effects in malignant melanoma.

Recently, peptides that offer versatility in drug discovery for the successful treatment of cancers have emerged. Peptide-drug conjugates (PDCs) represent an important therapeutic strategy for increasing tumor penetration and selectivity. We previously reported that M, which is extracted from bee venom, targets M2 macrophages and improves tumor treatment in lung cancer. M is an amphipathic peptide with 26 amino acid residues (AIGAVLKVLTTGLPALISWIKRKRQQ) that specifically binds to M2-like TAMs. Mertansine (DM1) is a strong cytotoxic agent that interacts with tubulin and inhibits the assembly of tubulin into microtubules. Because it targets microtubules and inhibits cell cycle, its clinical efficacy as a potential anti-cancer agent has been studied. However, meaningful results have yet to be obtained in clinical trials, with patients also suffering several side effects, such as myelosuppression. Antibody drug conjugates (ADCs) are currently the most successful type of drug conjugates, consisting of antibody (targeting), linker (linking the antibody to the payload), and Payload (killing target cells). Payload is a cytotoxic compound and is divided into microtubule inhibitors, such as DM1, and DNA-damaging agents, such as anthracyclines. DM1 alone has not been developed as a drug but is currently used as an antibody-drug conjugate. It has been reported that the peptide LLC2B combined with DM1 exerts an anticancer effect in breast and esophageal squamous cell carcinoma, suggesting it could be developed as a potential PDC for tumor treatment. In the present study, we investigated the anti-cancer effects of M-DM1, which was synthesized using M as a carrier for targeting TAMs and DM1 as a payload. We found that M-DM1 exerts its therapeutic effects by specifically depleting M2-like TAMs in a melanoma mouse model. Through the regulation of M2-like TAMs, M-DM1 induced a significant increase in the infiltration of effector cells, such as CD8 T cells and natural killer (NK) cells, into the TME. Collectively, our results suggest that depleting M2-like TAMs in the TME by treatment with M-DM1 has immunotherapeutic effects in malignant melanoma.

Recently, peptides that offer versatility in drug discovery for the successful treatment of cancers have emerged. Peptide-drug conjugates (PDCs) represent an important therapeutic strategy for increasing tumor penetration and selectivity. We previously reported that M, which is extracted from bee venom, targets M2 macrophages and improves tumor treatment in lung cancer. M is an amphipathic peptide with 26 amino acid residues (AIGAVLKVLTTGLPALISWIKRKRQQ) that specifically binds to M2-like TAMs. Mertansine (DM1) is a strong cytotoxic agent that interacts with tubulin and inhibits the assembly of tubulin into microtubules. Because it targets microtubules and inhibits cell cycle, its clinical efficacy as a potential anti-cancer agent has been studied. However, meaningful results have yet to be obtained in clinical trials, with patients also suffering several side effects, such as myelosuppression. Antibody drug conjugates (ADCs) are currently the most successful type of drug conjugates, consisting of antibody (targeting), linker (linking the antibody to the payload), and Payload (killing target cells). Payload is a cytotoxic compound and is divided into microtubule inhibitors, such as DM1, and DNA-damaging agents, such as anthracyclines. DM1 alone has not been developed as a drug but is currently used as an antibody-drug conjugate. It has been reported that the peptide LLC2B combined with DM1 exerts an anticancer effect in breast and esophageal squamous cell carcinoma, suggesting it could be developed as a potential PDC for tumor treatment. In the present study, we investigated the anti-cancer effects of M-DM1, which was synthesized using M as a carrier for targeting TAMs and DM1 as a payload. We found that M-DM1 exerts its therapeutic effects by specifically depleting M2-like TAMs in a melanoma mouse model. Through the regulation of M2-like TAMs, M-DM1 induced a significant increase in the infiltration of effector cells, such as CD8 T cells and natural killer (NK) cells, into the TME. Collectively, our results suggest that depleting M2-like TAMs in the TME by treatment with M-DM1 has immunotherapeutic effects in malignant melanoma.