Skin Cancer immunotherapies

Immunotherapies are ones that mobilize the body’s own immune system defense against disease processes.  This blog entry is about immunotherapies for skin cancers, focusing on an effective older one known as imiquimod or by its trade name aldara, and a partially effective newer one still in the approval process called ipilimumab.

About skin cancer immunotherapies

The concept of cancer immunotherapy goes back many years and has been of particular interest for treating deadly cancers for which no good conventional treatment exists.  Cancer immunotherapy is the use of the immune system to reject cancer. The main premise is stimulating the patient’s immune system to attack the malignant tumor cells that are responsible for the disease. This can be either through immunization of the patient (e.g. by administering a cancer vaccine, such as Dendreon’s Provenge), in which case the patient’s own immune system is trained to recognize tumor cells as targets to be destroyed, or through the administration of therapeutic antibodies as drugs, in which case the patient’s immune system is recruited to destroy tumor cells by the therapeutic antibodies(ref).”

Basal cell carcinoma immunotherapy

Imiquimod is a topical cream immunotherapy agent originally approved in the 1990s for the treatment of genital warts(ref)(ref)(ref).  It was later found to be effective in clearing up actinic keratoses (a possibly pre-cancerous condition of damaged skin) and superficial (non-penetrating) basal cell carcinomas.  As outlined in the 2010 publication New perspective in immunotherapy: local imiquimod treatment, imiquimod, known by its trade name Aldara, is largely a success story. “Imiquimod belongs to the family of synthetic small nucleotid-like molecules of imidazoquinolinamines. It is an immune response modifier with potent antiviral and antitumor effects, which are mediated by Toll-like receptors (TLR7 and TLR8). Imiquimod targets predominantly TLR7 expressing plasmacytoid dendritic cells and Langerhans cells, with secondary recruitment and activation of other inflammatory cells. Activation of TLR7 results in the stimulation of the innate and acquired immune responses, in particular cell mediated immune pathways. Topical imiquimod cream 5% (Aldara, MEDA Pharma) has been found to be effective for the treatment of actinic keratoses, superficial basal cell carcinoma and anogenital warts. Topical imiquimod is especially recommended for the treatment of large clinically asymptomatic fields containing tumor cells (“field cancerization”). Treatment with imiquimod applied at home by patient gives excellent cosmetic results. There are some data on its efficacy in nodular basal cell carcinoma and in some other skin cancers. The drug appears to be well tolerated with mild to moderate to local inflammation at the site of application. This paper provides a review about current experience and possible future development of imiquimod.”

Imiquimod was approved in 2004 by the FDA for use with patients having a normal immune system and who have superficial basal cell carcinoma – one of the four types of basal cell carcinoma.   It is approved for application to tumors with a maximum diameter of 2.0 centimeters, and use is limited to certain areas of the body.  For tumors in areas like the face or for larger areas where multiple small tumor sites may be involved(ref), use of imiquimod can be an attractive alternative to surgery.  The 2006 paper Use of 5% imiquimod cream in the treatment of facial basal cell carcinoma: a 3-year retrospective follow-up study reports “We found that 5% imiquimod cream is an effective treatment option for superficial and nodular basal cell carcinomas, giving a clearance rate of 89.5% at an average of 39 months of follow up.”

I need to disclose that I was treated for a superficial basal cell carcinoma on my face using 5% imiquimod cream about 4 years ago and after a few months of treatment the cancer was permanently gone.  Also, a biopsy four weeks ago showed that another small sore on my face was a basal cell carcinoma.  I doubled up on my morning curcumin and other anti-inflammatory supplements and a second biopsy on the same spot 12 days later showed actinic keratoses but no signs of basal cell carcinoma.  Nonetheless, with the help of my understanding dermatologists, I have just-in-case commenced a new round of treatment on the spot using imiquimod.  This is personal anecdotal data that may or may not be relevant to others.  Please see the medical disclaimer for this blog. 

Melanoma immunotherapies

The story of immunotherapies for melanoma is much more of a mixed one.  The 1992 publication Immunotherapy with monoclonal antibodies in metastatic melanoma opens with statements that could be still written today: “Therapy for metastatic melanoma has been disappointing to date. Treatment with chemotherapy only uncommonly results in complete responses and rarely results in long-term survivors.”  The abstract of the publication goes on to say “The identification of human melanoma cell surface antigens has led to the development of an array of mouse monoclonal antibodies (MAb) for use in the diagnosis and therapy of patients with metastatic melanoma. Strategies utilizing MAbs based on immunologic approaches have been developed. Naked MAbs directed against glycoprotein surface antigens or conjugated to toxins or radionuclides have shown little biologic or clinical activity. However, phase I studies of MAb directed against glycolipid antigens have yielded objective tumor shrinkage with occasional complete responses. Severe toxicity has been seen infrequently. Possible anti-tumor mechanisms include complement activation and antibody-dependent cellular cytotoxicity utilizing natural killer cells or monocytes as effector cells. Strategies to enhance the anti-tumor effects of MAb, including combinations with cytotoxic agents and cytokines, have been introduced with limited success thus far. The development of a human IgG anti-mouse antibody has been seen in nearly all treated patients. A new generation of MAb engineered to overcome the immunogenicity of mouse MAb and to enhance immune effector function will soon enter clinical trials.”  Yet, despite the sounded note of optimism, progress now 18 years later has been tortuously slow.

The May 2010 blog entry Melanoma Research Update discusses the long and mostly-dismal history of clinical trials for melanoma and an April 2010 publication on a PhaseI/Phase2 trial of using autogolous denditric cells as a melanoma immunotherapy, Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial.  I said “I decode this (the results) to mean that about a quarter of the treated patients extended their mean survival time from 9 months to 18.4 months.  While this is only a Phase I/II study, it casts doubt on whether dendritic cell cancer immunotherapy, a major focus of current cancer research, will provide a magic bullet against aggressive cancers.”  This still seems to be the case.

A little more than a month ago, a new report appeared on a Phase III clinical trial of a monoclonal antibody treatment against melanoma.  The June 2010 publication in the New England Journal of Medicine Improved Survival with Ipilimumab in Patients with Metastatic Melanoma describes Phase III clinical trial results for ipilimumab, an immunomodulatory monoclonal antibody that targets cytotoxic T-lymphocyte antigen 4 (CTLA4).  “A total of 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136).” (gp100 is a glycoprotein peptide vaccine)   — “The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76)(ref).”The good news is that, for patients with advanced melanoma who were virtually certain to die soon, the ipilimumab treatment increased survival by an average of 3.7 months.  Also, ipilimumab alone or in combination with a glycoprotein peptide vaccine improved the statistical probability for prolonged survival.  In study, ipilimumab provided durable disease control in 20-30 percent of patients and improved two-year survival.  – “These study results finally provide good news to the many researchers and clinicians who have faced disappointment for decades in treating a disease for which average survival is just six to nine months,” he (Dr. O’Day, who reported on the work) says. “The improvement in median survival associated with ipilimumab is impressive, but it is equally impressive that its benefit for improving survival appears to be persisting, with the longest available follow-up now out to 4.5 years(ref).”

Ipilimumab is still awaiting FDA approval which may take a year.  In the interim the drug is being offered to eligible recipients in a “compassionate use” trial at St. Luke’s Hospital cancer center(ref).

The bad news, of course, is that ipilimumab falls far short from being a cure for melanoma.

Besides monoclonal antibody treatments like ipilimumab, two other kinds of immunotherapy  are being used to treat melanoma: Cytokine therapy (interferon, interleukin) and Monoclonal antibody therapy. From the SkinCancerNet article Immunotherapy: What It is and How It Can Help Fight Cancer:  Cytokine Therapy: “Cytokines” are proteins released by cells in the immune system that help boost immunity. Two cytokines have been approved by the FDA for the treatment of metastatic melanoma: Interferon-alpha and Interleukin-2 (IL-2. — In clinical trials, these two cytokines have helped shrink tumors in about 10% to 20% of patients with stage III and stage IV melanoma. It is believed that cytokines hold enormous potential for cancer therapy, and many cytokines are being studied in clinical trials because of their ability to enhance the body’s immune response to cancer cells. – Interferon. Interferons are substances within the immune system that are produced in response to infection. They are classified as alpha, beta, or gamma forms — depending on the chemical structure, biologic activities, and other criteria. Interferon-alpha is FDA-approved for treating melanoma in stage IIB (primary tumor is 4 millimeters or more) and stage III (spread to the lymph nodes) when used along with another therapy, such as surgery. In these stages, interferon-alpha helps prevent recurrence and increases the likelihood that all cancer is eliminated.”

Up to this point, after some 20 years of research and development, melanoma immunotherapies only work in some patients and produce only partial results.  Meanwhile, the quest for better immunotherapy or combination immunotherapy treatments for melanoma goes on.

Much additional information relating to melanomas and emerging melanoma treatments are in the earlier blog post Melanoma Research Update.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career. I have been at this part-time for well over a decade, and in 2007 this became my mainline activity. In earlier reincarnations of my career. I was founding dean of a graduate school and a university professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at and an extensive site of my art at Please note that I have recently changed my mailbox to
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20 Responses to Skin Cancer immunotherapies

  1. liew says:

    I gathered Cansema is a good cancer skin cream for Melanoma, that it will eats away the cancer part and the wound will heal itself.

    Cansema for human use is both banned in the US and Australia. In Australia it is allowed for animal use and can be obtained from two sources. One source has a website that this cream is called Centreforce Black Salve for Cats, Dogs & Horses, available in two sizes. Human can use it too.

    About the ingredients

    History of development of Cansema

    Seeing this instruction would prepare one what to expect and how to manage the wound healing.

    It may be wise for big Melanoma to also order on the same website, Centreforce Silver Aloe Healing Creme, to help with wound healing.

    For Melanoma who has spread to the organs & bones, see the inspiring book, Cancer Jail – Death Row by Barry Thomson, a melanoma survivor. That is the book I first came across cansema. In the book, apart from melanoma, there are many healing methods for various cancer and also prevention.

    The following website seems to offer the cheapest price for this book (price in Australian dollars, excluding tax)

    If one is considering getting rid of Melanoma tumor, it may be wise to take something to kill off any tumor cells who may have spread in the body, (e.g. lymphatic system). Though I am not sure about Melanoma but other cancer tumor growth there is what is consider a primary growth. That is when some cancer cell has spread from the primary tumor, it is inhibited by the primary tumor to grow new blood vessels, hence making it dormant. But once the primary tumor is removed those microscopic tumors suddenly grows and you may have an explosion of metastatic growth in very short time. (source of info from Health Sciences Institute, vol 14, no 4; “Choking weed starves tumors by cutting off blood supply”.

  2. liew says:

    Having now obtained what seems to the original cansema distributed by Alpha Omega Laboratories, Guayaquil, Ecuador, the version of cansema from bevanpotter only share some of the ingredients.

    Ingredients from Alpha Omega Laboratories:

    Sanguinara, Nordihydroguauretic acid (NDGA, from Larrae Tridentata), Purple Lapacho, Red Clove, Water, Chaparral, Phytolacca, decandra, Rumex Acetosella and Zinc Chloride.

    The cansema also came with a more informative booklet then bevanpotter. Among a list of photos showing the before and after treatment there is one a gentlement who receive a treatment at the Hoxley clinic in dallas, Texas, 1973. That person who lives in phoenix, arizona is the grandfather of the distributor in Australia – Jennifer Wilson, where I obtained my cansema. There is no website for her and she only accept payment from postal money order.

  3. admin says:

    Thanks for the contribution. Of course in this blog as a policy, I cannot endorse the use of such alternative solutions for cancer and instead focus on reporting on relevant research. I would like to see carefully-executed research studies relating to the safety and effectiveness of cansema. Can you point me to any? If none exist, the substance remains as yet-another on a very long list of unproven and mostly-discredited cancer “remedies.”

  4. liew says:

    I understand why a product not backed by scientific studies cannot be endorsed in this blog. It is interesting to note in the following link a supposedly statement by Dr. Brian O’Leary, a former NASA astronaut who had used cansema

  5. liew says:

    Here is an interesting news from researchers of University of Western Australia using a special formulation of tea tree oil to treat non-melanoma skin cancers & precancerous lesions.

    (not recommend to use Tea tree oil from the shop for skin cancer)

  6. liew says:

    Following reference may be of interest:

    Annarica Calcabrini, Annarita Stringaro, Laura Toccacieli, Stefania Meschini, Manuela Marra, Marisa Colone, Giuseppe Salvatore*, Francesca Mondello†, Giuseppe Arancia and Agnese Molinari. Terpinen-4-ol, The Main Component of Melaleuca Alternifolia (Tea Tree) Oil Inhibits the In Vitro Growth of Human Melanoma Cells. Journal of Investigative Dermatology (2004) 122, 349–360.

  7. admin says:


    Regarding your comment just above this one, very interesting. The link to your citation is

    What appeared to be needed as a next step is in-vivo experiments in mice to see if a topical tea-tree oil based anti-melanoma ointment might be effective in eliminating melanoma lesions. A 2010 paper Inhibition of established subcutaneous murine tumour growth with topical Melaleuca alternifolia (tea tree) oil (at reports on such an experiment. “METHOD: Topical TTO formulations applied to immunocompetent tumour-bearing mice were assessed for antitumour efficacy by monitoring tumour growth and by histological analysis following treatment. — RESULTS: Four, daily, topical treatments of 10% TTO/DMSO regressed subcutaneous AE17 mesotheliomas in mice for a period of 10 days and significantly retarded the growth of subcutaneous B16-F10 melanomas. The antitumour effect of topical 10% TTO/DMSO was accompanied by skin irritation similar to other topical chemotherapeutic agents, but unlike other approved topical agents, quickly and completely resolved. Furthermore, we show that topical 10% TTO/DMSO caused an influx of neutrophils and other immune effector cells in the treated area, with no evidence of systemic toxicity. —
    CONCLUSION: TTO combined with an effective carrier significantly inhibited the growth of aggressive, subcutaneous, chemo-resistant tumours in immunocompetent mice. Taken together, these findings highlight the potential of topical TTO as an alternative topical antitumour treatment.” I would like to see further research along these lines, including research that shows complete cures of skin cancers.

    Because melanomas are potentially deadly, at this point I need to point out that self-treatment with tea tree oil is probably a dangerous thing to do.


  8. admin says:


    Regarding your first comment above, it is interesting that the February 2019 oublication I quote from in the coment above “significantly retarded” the growth on certain mouse melanomas while the June 2010 press release you mention reports that solid tumors vanished in 3 days. It is not clear that these were melanomas. In any event it is interesting that the Australian researchers are planning a clinical trial and this may tell us a lot. Thanks for your contributions.

  9. liew says:

    I think they are referring to non-melanomas tumors. The researchers are currently planning to get 50 persons for the trail.

  10. admin says:


    Right. I agree there is a possibility of another topical treatment for basal cell carcinomas based on tea tree oil. We shall see.


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