C3d Immunotherapies, A Novel Platform to Treat Cancer

a treatment for multiple myeloma and related conditions

As human life expectancy increases, there is an increase in the cases of diseases impacting older patients. One such disease is Multiple Myeloma (MM), a cancer of plasma cells found primarily in the bone marrow. MM has a median survival of just over five years. Despite significant advances in therapy, there is still no cure for MM because of current limitations in the standard of care, including extreme toxicity, severe drug complications, drug resistance, relapse, high cost, and lack of therapy for patients who develop full MM.

University of Michigan’s Marilia Cascalho, M.D., Ph.D., has identified C3d as a potential novel therapy for MM. C3d is a natural peptide and does not evoke an anti-C3d immune response that would limit its function. Additionally, C3d acts locally and has not been associated with toxicity, making C3d an ideal candidate to treat both elderly, weakened patients and relatively healthy patients with early-stage MM.

“C3d immunotherapies could be the cure for Multiple Myeloma,” says Cascalho. “If efficacy and lack of toxicity of C3d therapy in pre-clinical models translate into the human disease, C3d could be the treatment that is needed and become the new standard of care for Multiple Myeloma patients.”

Significant Need

Multiple Myeloma remains an incurable disease. Although there are high response rates to standard therapies, including autologous stem cell transplantation, alkylating agents, proteasome inhibitors, immunomodulatory drugs, and corticosteroids, most MM patients develop resistance to therapy and relapse. Even novel strategies still result in limited patient response, significant toxicities, and recurrence of disease.

Compelling Science

Free C3d (a catalytical inactive fragment of the complement C3 protein) generate robust cell-mediated immunity to antigens endogenous to tumor cells.

Pre-clinical data suggests that C3d peptide will overcome current MM therapy limitations due to several unique properties of the technology: C3d augments endogenous anti-MM immunity by targeting the very elements that limit anti-tumor immunity. Thus, C3d interrupts the checkpoint inhibitor axis by decreasing PD-1 /PD-L1 expression and by inducing apoptosis of T regulatory cells. First clinical trials are anticipated to target drug-resistant relapsed refractory MM (RRMM).

Competitive Advantage

C3d acts locally and has not been associated with toxicity, making it an ideal candidate to treat a more significant percentage of patients with MM. Additionally, C3d efficacy does not require previous knowledge of tumor antigens compared to competitor targeted immunotherapies.

Overall Commercialization

  • Intellectual Property: Patent for “C3d cellular and acellular vaccines for the prevention and treatment of cancer”
  • Commercialization Strategy: Technology may either be licensed or become part of start-up. Follow-on funding is being pursued.
  • Regulatory Pathway: Preparing IND application for FDA and manufacturing the human prototype product
  • Product Launch Strategy: Obtain Investigational New Drug approval and plan clinical trials.


  • Optimization of C3d peptide therapies in pre-clinical models
  • C3d therapy to treat spontaneous MM in Vk*-MYC animal models
  • C3d peptide therapies vs. standard of care therapies to treat MM
  • C3d therapy to treat drug-resistant RRMM
January 28, 2022