1. What is LIFT cancer treatment?
LIFT is the abbreviations of Leukocyte Infusion Therapy, a new cancer treatment that will transfer naturally-occurring cancer-killing activity (CKA) in the granulocytes of a selected donor into the body of a cancer patient.
2. The discovery process of LIFT Therapy:
In 1999, scientists encountered a unique mouse that refused to succumb to repeated challenges with lethal cancer cells that uniformly killed all other laboratory mice, even at much lower doses. Further studies of this phenotype reveal that this unusual cancer resistance is inheritable and entirely mediated by the macrophages and neutrophils of the innate immunity. Transfer of leukocytes with this high level of cancer-killing activity (CKA) from these cancer-resistant mice cures the most aggressive advanced cancers in other mice without any side effect. Most surprisingly, a similar activity of killing cancer cells was discovered in the granulocytes and monocytes of some healthy people.
Additional studies also indicate that CKA is highly dynamic in human populations. CKA is affected profoundly by individual genetic make-ups, by different seasons, by different ages and by emotional stresses. More importantly, low CKA has a significant association with cancer patients in comparison to healthy people. It seems reasonable to believe that cancers can be treated by transferring granulocytes, an abundant white cell fraction that contains the most CKA, from cancer-resistant human donors to cancer patients. This new therapeutic concept is significantly different from the conventional immunotherapies based on the attempts to revive cancer patients’ own adaptive immunity to fight their own cancers.
Drs. Cui and Willingham began following the line of research that led to LIFT when, quite unexpectedly, they found a single mouse who repeatedly survived injection of cancers that were known to be lethal in all other mice. Subsequent research found that some offspring of this mouse also inherited its natural immunity to cancer, and that this cancer-fighting property could be transferred to other mice through a transfusion of certain white blood cells.
The researchers state that humans also possess these special cancer fighting cells, but their effectiveness is highly variable between individuals. Their ability to ward off cancer can be affected by such factors as genetics, age, seasonality, and stress levels. By taking granulocytes, the portion of human leukocytes with the highest cancer fighting activity, from the most cancer-resistant donors and injecting them into people with aggressive cancer tumors that have previously proved unresponsive to other therapies, Dr. Willingham says the Wake Forest Team hopes to prove that this Leukocyte InFusion Therapy (LIFT) can "be another arrow in the quiver of treatments aimed at cancer."
Granulocytes are the most abundant type of white blood cells and can account for as much as 60 percent of total circulating white blood cells in healthy humans. Donors can give granulocytes specifically without losing other components of blood through a process called aphaeresis that separates granulocytes and returns other blood components back to donors.
The doctors speak of their hope for clinical benefit and measurable efficacy for the treatment of cancer in humans with LIFT. Dr. Cui points out, however, that a wide variety of the most aggressive cancers were completely cured with this approach in mice
(Picture Above: The cancer-resistant mice all stem from a single mouse discovered in 1999. "The cancer resistance trait so far has been passed to more than 2,000 descendants in 14 generations," said Cui, associate professor of pathology. It also has been bred into three additional mouse strains. About 40 percent of each generation inherits the protection from cancer.) The original group of cancer-resistant mice, also described in Proceedings of the National Academy of Sciences, successfully fought off a range of virulent transplanted cancers. With the US FDA approval, Leukocyte blood component transfusion to improve anticancer immunity has now entered a phase II clinical trial phase of treatment. (United States FDA Clinical trials Web site LIFT Clinical trials registration)
3. Granulocyte introduction
(Video 1: shown the process of the granulocyte white blood cell terminating the cancer cells. Arrow indicates a large size cell as cancer cells, surrounding small cells are granulocytes terminating the cancer cells. Once granulocytes enter patients with cancer, like the" precision-guided missiles ", that automatically precisely lock the cancer cells, and quickly gathered around the cancer cells to perform the termination process）
Granulocytes are the most abundant type of white blood cells and can account for as much as 60 percent of total circulating white blood cells in healthy humans. In human blood contains red blood cells to transport oxygen and immune function of white blood cells, granulocyte is the largest human white blood cells, the lowest life expectancies, strongest regeneration ability, fastest mobility, with the highest force group of immune cells.
Features of Granulocyte?
Granulocyte's main function is to resist bacteria and cancer cells. Granulocyte is the first line of defense of the body's immune system, is the most common kind of aggregation of immune cells in the tumor. When the organism is malfunction, granulocyte parts would be the first to reach the lesion, wound infection or tumors, primarily using large numbers of cytotoxic granules in their cytoplasm, anti-pathogenic cells through the release of cytoplasmic granules, identification and specificity of anti-bacteria and cancer cells. Granulocyte is not only the new scientific research has found to treat diseases of the immune system, can also be used to increase the antitumor immunity in cancer patients, to kill cancer cells, is a major breakthrough in modern biotechnology techniques.
(Picture: shown how cancer cells in mice was in the process of killing and shooting to the left as “ Petal ”, in which “ Balm ” Parts are the cancer cells, is surrounded by granulocytes, granulocyte gathered to the cancer cell surface, close contact with the cancer cell surface, resulting in a confined space, and to kill cancer cells.)
4. Introduction of “LIFT Therapy”
Granulocyte is the innate immune system and an important component of cells in the immune system, with natural anti-cancer behavior, and those with highly active granulocyte are able to kill cancer cells. Although, many human possessed white blood cells which also carry granulocyte anticancer however due to the low activity level these cell are not strong enough for cancer fighting activity. The key to the success for the new therapy is to transfuse sufficient granulocytes from healthy donors while their cancer-killing activities are at their peak level.
The therapy technology of key is, a pheresis machine separates donor granulocytes from other blood products that will be immediately returned to donors so that the health impact on granulocyte donation is much smaller than on whole blood donation. Granulocyte mobilization and collection by apheresis have been used in clinical practices for a long time with very good safety record.
5. Safetyness of “LIFT Therapy”
Granulocyte transfusions have been used in clinical practice for more than 30 years to treat patients who have life-threatening infections and have very low white cell count following chemotherapy. In that setting, granulocyte infusions are given to help the patients fight infections. In this clinical trial granulocyte infusions are given to hopefully help you fight cancer. Granulocytes blood component transfusion improve anticancer immunity therapy anticancer treatment using just the way of the granulocytes component blood transfusion, not only quick and easy, with positive clinical efficacy, and proven that the use of the granulocytes blood component transfusion improve anticancer immunity therapy " are equally safe.
6. Features of “LIFT Therapy”
A. Proven the human body contain concentrations of granulocyte has anti-cancer
B. Discovery of granulocytes natural immunity to cancer cancer-fighting property could be transferred to others through a transfusion of certain white blood cells.
C. Discovered a technology to screen granulocyte from healthy donors with highly effective cancer-fighting property of granulocyte.
D. Explored a way for the granulocytes to replace the failure cells in cancer patients to take advantage of the healthy human body cells with efficient anti-cancer activity, so as to achieve the anti-cancer effect.
E. Explored the best time and seasons with the use of granulocyte for anticancer treatment.
F. Explored the best dosage for the use of granulocyte anti-cancer therapy.
G. With the shorter period than the conventional therapies in the treatment of cancer.
7. What to expect before receiving LIFT treatment?
Patients will first visit the related website for more information with further understanding of such treatment .
With the oncologists from the hospital screening of patients with doctors pre-approval, review of applications of each potential patient for“Granulocytes blood component transfusion improve anticancer immunity therapy ”, filter out if the therapy is suitable for the treatment of the cancer patient .
Due to the variety type of cancers, with different stages of cancer, no conditions are alike. Therefore, "Granulocytes blood component transfusion improve anticancer immunity therapy" may not be suitable for all cancer patients.
And for patient, who is responsible to provide the most detail medical history and most up-to-date medical treatment record, so that “Granulocytes blood component transfusion improve anticancer immunity therapy” for best achievement of therapeutic result.
Some of your blood will be sent to a research laboratory to evaluate how well your body has accepted the blood cells from your donor. The blood will be collected prior to beginning treatment.
Once doctors confirmed if patient can undergo with “Granulocytes blood component transfusion improve anticancer immunity therapy” the team will find the matching granulocyte donors. Once donor is verified, patient will be arranged for immediate hospitalization with treatment date. The treatment period is about 20 – 30 days.
During the treatment, dosage will be determined in accordance with condition treated with granulocyte. For the blood transfusion during treatment does not require anesthesia.
Thorough medical monitoring and tests are necessary after each blood transfusion made.
Although you may be discharged from the hospital, however, doctor will require patient for a revisit on a regular basis. Some patients may require a longer period for further observation.
During the observation period after patient discharged, the patient is required to follow doctor's instructions for possible medical treatment and medication. Any unauthorized treatment or medication by authorized physician may result negative result.
Questions and Answers:
1. What’s the effective rate of “LIFT Therapy” ?
From previous cases of “granulocytes blood component transfusion improves anticancer immunity therapy”, the curative rate is promising. The therapy is transfer the healthy human granulocyte to cancer patient, will significantly improve antitumor immunity in cancer patient to help cancer patients fighting and killing the cancer cells. Granulocyte access to cancer patient can accurately identify and kill cancer cells within a few hours, with no side effect on normal cells.
2. Were there any clinical cases practicing this therapy?
This treatment has been practicing in US clinically for more than 20 cases. Many patients can be clearly observed with the positive effects of granulocyte killing cancer cells, the uses of the therapy of prospects are very broad. Moreover, all cancer patients treated with granulocyte, shown with no metastasis, which cannot be promised with any other treatment options these days.
3. How lung cancer (or other cancers) suit for this treatment?
Although such therapy shown a very promising enhancement of anticancer immunity in patients, however, with the evaluation from our specialist it is suggested for patients to perform any necessary tumor removal surgery before undergo treatment.
4. I was undergo with radiation therapy about 6 months ago. Is it possible for me to undergo LIFT treatment as a follow-up or secondary treatment?
Depending on your situation, “Granulocyte blood component transfusion improves anticancer immunity therapy” can be a secondary treatment. As we all known, radiotherapy, chemotherapy or traditional surgery may not completely terminate or kill all the cancer cells, “Granulocyte blood component transfusion improve anticancer immunity therapy " can be more effectively identify and track fragmentation of cancer cells and kill them. You can discuss with our specialist, for further confirmation if your condition is the applicable for the therapy.
Although it is shown with positive clinical result of our treatment however, it is our responsibility to carefully select and screen the appropriate patient to undergo with such treatment.
5. What are the side effects and negative responses?
The cancer patients will receive the granulocytes through a transfusion – a safe process that has been used for more than 30 years. Normally, the treatment is used for patients who have antibiotic-resistant infectious diseases. The treatment will be given for three to four consecutive days on an outpatient basis. Based on observation of clinical treatment, after transfusion of the granulocyte, granulocyte start kicking in with the cancer cells, which might give patient with flu-like symptoms, such as fever, chills, but soon be self-recovered. Some patients, after the kick in of the granulocyte anti cancer cells effect, might rarely come across tumor lysis syndromes, probably after 10 days of treatment take place. That shall require special treatment by doctors, therefore, it is always prefer that a patient to stay for at least 20 days of hospitalization for better observation , to monitor of your possible sickness and complications at any time.
6. How long is the treatment period?
According to the severity of the condition and the type of cancer, the different cycles of therapy to be applied, generally speaking from 20 to 30 days. A post treatment period is strongly suggested, which will require patients to return for check up on a regular basis.
7. Will cancer reoccur after treatment?
It has a variety of factors to cause cancers, with the traditional methods of treatment, including surgical removal, radiation therapy, chemotherapy, are unable to 100% ensure without recurrence after treatment. “granulocyte blood component transfusion improve anticancer immunity therapy " is a component of the therapy using blood transfusions which significantly improve the anti-tumor immunity in patient, however, there is no guarantee so far that any cancer will not reoccur after treatment. Therefore, we usually recommend that repeat with 2~3 treatments a year.
8. How much is this treatment costs?
In general a simple particle cells for the treatment of patient, is about USD$30,000. Including hospitalization and basic medical care costs. Which do not include other medical cancer treatment costs such as ICU etc.
We will be communicating with you at any time according to your particular situation. Before your admission, an initial deposit of USD$10,000 is require. And, we shall be discussing with you before any possible charges will or can be made with such deposit.
9. How soon can I start with the treatment?
We need to screen and filter cases, such as your blood type, and commutate with matching donors for any pre-treatment preparation. After receiving your initial deposit and confirmation of your schedule, you will be required to provide us the most up-to-date PET/CT for an assessment evaluation.
Here's how the LIFT treatment works:
* Donor selection: Healthy young volunteers will be screened for the level of CKA, blood types, HLA types, infectious disease status, CMV status etc. by blood tests and physical examinations. The selected volunteers will become part of the Donor Registry. The test results of selected volunteers will be used to match with specific patients.
* Granulocyte collection: When a qualified patient is identified for treatment, granulocytes from several matched donors in the donor registry will be mobilized by two medications and collected by a well-established medical procedure called "apheresis" or "pheresis." A pheresis machine separates donor granulocytes from other blood products that will be immediately returned to donors so that the health impact on granulocyte donation is much smaller than on whole blood donation. Granulocyte mobilization and collection by apheresis have been used in clinical practices for a long time with very good safety record.
* Patient selection and granulocyte infusion: Qualified patients will be selected according to general health condition, disease status and match criteria. Freshly collected granulocytes from matched donors will be given to patients via IV infusion.Granulocytes cannot be stored or shipped for later uses.
Granulocyte infusion therapy has been traditionally used for treating neutropenia-related infections for over 30 years with excellent safety records. Since a significantly higher dose of granulocytes for each patient is proposed in our new cancer treatment, the primary goal of this clinical trial is to test whether the recipients can tolerate the proposed dose of granulocytes.
The main focus of the trial is the possibility of developing Transfusion-Associated Graft vs Host Diseases (TA-GVHD) and other potential side effects in the study subjects at higher doses of donor granulocyte.
Donor granulocytes per se are not known to produce TA-GVHD. However, granulocytes collected via apheresis may contain with some donor T-lymphocytes that in some rare occasions can produce various degrees of TA-GVHD in some individuals, especially the recipients with immune suppression. If possible, we will also make observations on the efficacy of this treatment on the study subjects with measurable diseases of cancer. We will recruit 22 cancer patients as study subjects for this trial.
SFBMSCTI IND approval letter for LIFT treatment Trail
References
1. Cancer "Cure" in Mice to be Tested in Humans. From press materials provided by Wake Forest University Baptist Medical Center through Newswise, retrieved June 26, 2008
from http://www.newswise.com/articles/view/542007/
2. White Blood Cells of Cancer-Resistant Mice Overwhelm Natural Defenses of Cancer Cells, Wake Forest University Baptist Medical Center, retrieved June 26, 2008.
from http://www1.wfubmc.edu/News/NewsARticle.htm?ArticleID=1972
3. Cui, Zheng. Abstract. Retrieved from Understanding Aging: Biomedical and Bioengineering Approaches, The Methuselah Foundation, on June 28, 2008.
from http://www.methuselahfoundation.org/UABBA/speakers/cui/
4. White Blood Cells From Cancer-Resistant Mice Cure Cancers In Ordinary Mice ScienceDaily on May 9, 2006.
from http://www.sciencedaily.com/releases/2006/05/060509094714.htm
Clinical Study References
Novel innate cancer killing activity in humans
Blanks et al. Cancer Cell International 2011, 11:26 
The winding road to the discovery of the SR/CR mice
Cancer Immunity, Vol. 3, p. 14 (16 October 2003)
Spontaneous regression of advanced cancer: Identification of a unique genetically determined, age-dependent trait in mice
PNAS May 27, 2003 vol. 100 no. 11
The effect of aging on cellular immunity against cancer in SR/CR mice
Cancer Immunol Immunother (2004) 53: 473–478
Halo naevus: a visible case of immunosurveillance in humans?
The Lancet, Oncology Vol 5 July 2004 http://oncology.thelancet.com
Effector mechanisms of the anti-cancer immune responses of macrophages in SR/CR mice
Cancer Immunity (31 October 2006) Vol. 6, p. 11
Transferable anticancer innate immunity in spontaneous regressioncomplete resistance mice
www.pnas.orgcgidoi10.1073pnas.0602382103
RTehseaerc hs aprtieclectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction
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Department of Health and Human Services
Investigational New Drug Application (IND) for "Allogeneic Human Granulocytes" Approval Letter
RCesaeanrcch eartric lreesistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements
Sanders et al. BMC Cancer 2010, 10:121 http://www.biomedcentral.com/1471-2407/10/121
Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice
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Chemokines Acting via CXCR2 and CXCR4 Control the Release of Neutrophils from the Bone Marrow and Their Return following Senescence
Immunity, Vol. 19, 583–593, October, 2003, Copyright 2003 by Cell Press