Anticancer Peptides (ACPs) Development Services
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Anticancer Peptides (ACPs) Development Services

The introduction of targeted therapies has changed the strategies used in treating cancer because they are more precise and less harmful when compared to older methods like chemotherapy and radiotherapy. A very encouraging approach is the application of anticancer peptides (ACPs). At Protheragen, we have a full array of development services for ACPs that include every step of the R & D process.

Overview of Anticancer Peptides (ACPs)

Anticancer Peptides (ACPs) are a class of peptides with unique anticancer properties, which include targeted and selective cell membrane disruption of tumors. These cytotoxic peptides are able to hydrolyze cancer cellular membranes because of their specific structures. Most of them have cationic residues, which are positively charged and therefore aid in binding to the negatively charged surface of the cancer cells. Unlike traditional anticancer drugs, ACPs allow for healthier tissues to remain unharmed. With this mechanism of action, the collateral damage and consequences of conventional cancer therapeutics are considerably less.

Key Characteristics of ACPs

  • Selective Targeting: By design, ACPs bind to the outer membranes, and some even dock to the intracytoplasmic parts of cancer cells, which makes them highly selective.
  • Small Size and High Penetration: The small molecular size of ACPs makes it easier for them to penetrate the membranes of the cancer cells when compared to larger drug molecules.
  • Easily modified: The therapeutic effectiveness and specificity of ACPs can be altered to make them more clear-cut and effective by making them more stable chemically.
  • Minimal Toxicity: Compared to conventional chemotherapy agents, ACPs exhibit reduced systemic toxicity, which results in fewer side effects.
Mechanism of action of antitumor peptides.Fig.1 Anticancer peptide mechanisms of action: mitochondrial-associated pathways and death-receptor-induced pathways. (Karami Fath M., et al., 2022)

ACPs in Cancer Therapeutics Development

  • Targeted Cancer Therapy
    ACPs can be utilized as molecularly targeted peptides, which means they are created to selectively attach to cancer cells or organelles located within the cells. For instance, defensins, lactoferricin B, and magainin-2 peptides have been documented to selectively bind to and attack only the cancer cells. These peptides kill the cell through the following mechanisms:
    -Membrane destruction: ACPs actively permeabilize and disrupt the integrity of cancer cells' membrane-bound systems.
    -Immune response suppression: Some ACPs have been shown to stimulate the immune system by boosting the release of cytokines or activating NK cells, which are more harmful to the cancer cells.
  • Immunotherapy
    The role of ACPs in immunotherapy is still developing. Certain ACPs serve as either cancer-targeting or drug-binding peptides that can shuttle drugs to malignant cells. These peptides can also stimulate immune responses, thus making them suitable for co-administration with checkpoint blockers or tumor vaccines.
  • Peptide Vaccines
    ACPs are being investigated as components of peptide-based vaccines. These vaccines utilize ACPs to provoke an immune response against malignant cells. Preclinical research and early-phase clinical trials have been conducted for melanoma, prostate, and breast cancer, and several ACP-based vaccines have shown promise.

Table 1. Examples of ACPs in clinical trials. (Chiangjong W., et al., 2020)

Phases Biological Peptides Conditions Outcomes
Early Phase 1 MUC-1 peptide vaccine, poly ICLC, MUC1 peptide-poly-ICLC adjuvant vaccine Breast cancer A positive anti-MUC1 antibody response
HER-2/neu peptide vaccine Breast cancer Peptide-specific interferon-γ producing T-cell and peptide-specific IL-5 producing T-cell responses
GAA/TT peptide vaccine and poly-ICLC Astrocytoma, oligoastrocytoma, glioma Induction of GAA-specific T-cell response, Infiltration of GAA-specific T-cells
Phase 1 Gag:267-274 peptide vaccine Melanoma Vaccine peptide-specific CTL response
HPV16 E7 peptide-pulsed autologous DCs Cervical cancer Pulsed autologous DCs immunotherapy
NY-ESO-1b peptide plus CpG 7909 and Montanide ISA-5 Cancer, neoplasm NY-ESO-1 specific humoral and cellular immunity
Antiangiogenic peptide vaccine Hepatocellular carcinoma Peptide-specific CTL response
RNF3-721 Colorectal cancer Specific CTL induction in vitro
LY6K, VEGFR1, VEGFR2 Esophageal cancer Immune responses including LY6K, VEGFR1 and VEGFR2 specific T-cells
HLA-A0201 or HLA-A0206-restricted URLC10 peptides Non-small cell lung cancer Immunological responses, including peptides specific CTL, antigen cascade, regulatory T-cells, cancer antigens, and HLA levels
Phase 1/Phase 2 MAGE-3.A1 peptide and CpG 7909 Malignant melanoma Detectable CTL response
VEGFR1-1084, VEGFR2-169 Pancreatic cancer Peptide-specific CTL response
HER2/neu peptide vaccine Breast cancer HER2-specific T-cell response
HLA-A2402 or A0201 restricted peptides Solid tumors Various immunological responses, including peptides specific CTL, antigen cascade, regulatory T-cells, cancer antigens, and HLA levels
Modified CEA peptide Pancreatic adenocarcinoma T-cell response with modified CEA peptide
Phase 2 Synthetic human papillomavirus 16 E6 peptide Cervical cancer Immunological response to HPV
gp100:209-217(210M), HPV 16 E7:12-20 Melanoma T-cell immunity to the gp100 peptide and E7 12-20 papillomavirus peptide
WT1 126-134 peptide Acute myeloid leukemia Generation of T-cell response
G250 peptide Metastatic renal cell carcinoma G250-specific CTL response
Melanoma helper peptide vaccine, multi-epitope melanoma peptide Melanoma CTL response, helper T-cells respond to 6MHP
Phase 3 PRI leukemia peptide vaccine Leukemia Immune response to PRI-HLA-A2 tetramer
Phase 4 Degarelix (LHRH antagonist) Prostatic neoplasms Binds to GnRH receptors and blocks interaction with GnRH

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen offers advanced ACP development services to meet the needs of any specific customer. Our clients do not need to worry about anything else if they wish to create a new peptide for a certain cancer or improve the efficacy of an existing peptide. Not only will our experts guide them through the process, but they will also offer complete solutions.

Peptide Discovery and Design

Our team uses advanced bioinformatics and computational modeling tools to design ACPs that target specific cancer cell markers. By analyzing the biological properties of cancer cells, we can identify potential peptide sequences that are most likely to be effective.

Peptide Synthesis and Optimization

Once the peptide sequences are identified, Protheragen synthesizes the peptides using solid-phase peptide synthesis (SPPS) techniques. We also optimize the peptides to improve their stability, half-life, and overall therapeutic potential. This may include modifying the peptide's amino acid sequence or incorporating non-natural amino acids.

Bioconjugation Services

We offer bioconjugation services, including peptide-drug conjugates (PDCs), peptide-antibody conjugates (PACs), and PEGylated peptides, to enhance the therapeutic properties of peptides. Our services involve the design, synthesis, and characterization of conjugates to improve stability, specificity, and efficacy. We provide comprehensive support for the development of bioconjugates tailored to specific therapeutic needs.

Preclinical Research

Protheragen provides full support during the preclinical research, including designing pharmacodynamics, pharmacokinetics and drug safety studies to assess how the peptides behave in the body.

Peptide FTE & FFS Services

Type Remarks
PDC Peptide - linker / payload Formats: Crude, desalted, salt-removed
Purity: 70%, >80%, >90%, >95%, >98%, >99%
Scale: Milligram to kilogram grade
Linear Peptides Synthetic peptides composed of up to 50 amino acids
Simple Modifications C-Terminus: amidation, acetylation, enzyme labeling
N-Terminus: acetylation
Complex Modifications Fluorescent labeling: Cy3, Cy5, Cy5.5, Cy7, FAM, FITC, Rhodamine B
Chelators: DOTA, DPTA, NOTA, DOPA
Cyclic peptides (1-to-2 disulfide, 2-to-2 disulfide, 3-to-2 disulfide bridges, click cyclization, thioether bridges, click + disulfide double cyclization, stapled peptides, etc.)
PEGylation
Unusual Amino Acids Peptides derived from unnatural amino acids

Protheragen assists in full ACP development, starting from the preliminary design stage to in vitro and in vivo testing. We have tailored our services to facilitate preclinical development for our clients so that they may progress with their projects in a timely and effective manner. If you are interested in our services, please feel free to contact us.

References

  • Karami Fath, Mohsen, et al. "Anti-cancer peptide-based therapeutic strategies in solid tumors." Cellular & Molecular Biology Letters 27.1 (2022): 33.
  • Chiangjong, Wararat, Somchai Chutipongtanate, and Suradej Hongeng. "Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application." International journal of oncology 57.3 (2020): 678-696.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.