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Editorial

CAN ALTERNATIVE TREATMENTS INDUCE

IMMUNE SURVEILLANCE OVER

CANCER IN HUMANS?

BACKGROUND

Saul Green

For decades, since first observing spontaneous tumor regressions in experimental

animals, scientists have debated the existence of a surveillance

role for the normal immune system (NIS) in regulating the growth and spread of

human cancer. 1 The observation led to the concept that through surveillance, the

NIS could detect and destroy newly formed cancer cells. This concept persists in

spite of the fact that 90% of the most common cancers, carcinomas, occur in a

host with a fully functioning NIS. 2 In addition, there is no good evidence of an

increase in common carcinomas in the presence of severely decreased immune

function . 3

Most public exposure to alternative medicine (AM) comes through popular

media, well-meaning friends and relatives, and books by AM practitioners and

proponents. One such book is Burton Goldberg’s Alternative Medicine; A Definitive

Guide to Cancer. 4 In the book, proponents claim that the immune system is

an innate “healing system,” and that cancer develops because the NIS is somehow

damaged or unable to carry out its “surveillance” role because of defective diet or

environmental toxins. Readers are offered reversal of such damage by detoxifying,

stimulating, rejuvenating, augmenting, and reactivating the defective NIS. A few

AM treatments recommended in the Definitive Guide are: Contreras metabolic

therapy with Laetrile, proteolytic enzymes, vitamins, minerals, coffee enemas

(p.126); homeopathy (p.147); Carnivora, extract of the Venus Flytrap plant

(p.60); I. Wm. Lane’s shark cartilage (p. 862); Burton’s Immuno-augmentive

Therapy (p.883); Wheeler’s “Autogenous Vaccine” (p.893); Siegel’s mind/body

treatment modalities (p.389); Munozi’s antimycoplasma autovaccine and re-

Saul Green, PhD, is the Science Editor of The Scientific Review of Alternative Medicine, former Professor of Biochemistry

at Sloan-Kettering Cancer Institute, and President of Zol Consultants, Inc., 340 West 57th Street, Suite

8J, New York, NY 10019.

THE SCIENTIFIC REVIEW OF ALTERNATIVE MEDICINE Vol. 4, No. 1 (Spring/Summer 2000)

6


Green: Can Alternative Treatmens Induce Immune Surveillance over Cancer in Humans? 7

moval of dental toxins (p.897); Spiegel’s emotional support and self-expression

therapy (p.459); and Gonzalez’s therapy including detoxification with coffee enemas,

dietary supplementation, and proteolytic enzymes (p.778).

THE REALITY OF IMMUNE SURVEILLANCE OF CANCER

The concept that the NIS watches out for and defends against cancer came

about as researchers were unraveling and defining the complex chain of reactions

that make up this system. 5 Immunologists demonstrated that the most common

cancers flourished in a host with a fully functional and competent immune

system. 6 In spite of this, many researchers, as well as “alternativists,” continue to

claim that a defective immune system is responsible in some way for development

of cancer. 7 The “alternativist” rationale is based on two assumptions. First, that

cancer cells are produced constantly or intermittently during life. Second, that

to protect the individual from a lethal outcome, the immune system must detect,

attack, and then destroy each cancer cell as it appears. 8

The Normal Immune System (NIS)

While cancers associated with viral infections arise rather quickly, most common

cancers develop over many years as the cells escape from normal intracellular control

mechanisms via multiple mutations. 9 Although tumor cells demonstrate abnormal

growth, they still display normal antigenic surfaces. Since the NIS is

programmed to recognize “non-self,” it does not “see” the tumor. 10

An immune response takes place when foreign proteins, i.e., antigens from

non-self cells—major histocompatibility complexes (MHCs) and other minor

antigens—are presented to T-cells. The hallmark of the NIS is its ability to respond

to this presentation. NIS cells have biochemical properties uniquely suited

to generate a large variety of individual receptor molecules (immunoglobulins)

and to select those that will be needed for further expression. Thus there exists

a seemingly infinite variety of specific receptors produced by immune system cells

to which foreign proteins can bind. 11

Only by externally manipulating the NIS pharmacologically or by injecting

manipulated products can an effective response be induced. 12 In spite of the

enormous amount of information amassed about the nature of the NIS and the

mechanisms by which it acts, immunotherapy still holds only a suggestion of

being able to control human cancer.

Natural Immunity

“Natural immunity” (NI) is immune activity not requiring deliberate immunization

by a foreign antigen. 13,14 The NI reaction differs from the NIS’s response to

protein determinants in that it is not dependent on transplantation antigens

found on foreign (non-self) cells. The NI response is due to nonspecific triggering

of the activity of cells like natural killer cells, macrophages, or polymorphonuclear

leukocytes (PMNs).

Dendritic cells (DCs) are thought to be sentinels of the immune system. 15,16

They originate in the bone marrow and are seeded into nonlymphoid tissues. DCs

capture and process exogenous antigens for presentation as peptide-MHC complexes

at their surface. They facilitate activation of natural killer (NK) cells. 17


8 THE SCIENTIFIC REVIEW OF ALTERNATIVE MEDICINE

The NI acts on antigens from infectious organisms and against some antigens present

in food or in the intestinal flora.

Because of their ability to attach foreign antigens and to present them to Tcells,

DCs are being considered for use as adjuvants for triggering an immune response

to cancer cells. 18 The program is something like the following: In order to

get the NIS to identify and attack the cancer, DCs would be generated in vitro

and antigenic material or DNA from the tumor would be attached to them. The

antigen-laden DCs would then be reinjected into the patient where they would

present the tumor antigen to T-cells. The hope is that through chronic infusion

of primed DCs, one can be immunized against one’s own cancer.

But there is also a problem of numbers. 19 The average number of cancer cells

present at detection of the primary or metastasis is between 1 × 10 9 and 1 × 10 12

cells. Each tumor cell would have to be contacted directly and destroyed by one or

more T-cells, and the required number for optimal cancer cell kill is unknown. Even

on a 1:1 (killer cell:tumor cell) basis, destruction would require 1 × 10 9–12 killer cells.

There are about 2–4 × 10 7 total T-cells normally present in an average human.

If enough primed T-cells could be mobilized, they would be diffused

throughout the body and there is no known normal mechanism to assure their

reaching a critical number of target cancer cells before dying or becoming deactivated.*

THE NIS AND THE MIND

Alternative” practitioners claim that the mind and “spiritual harmony” promote

“healing” by stimulating the activity of the NIS. Their literature asserts that virtually

every psychological variable influences NIS surveillance. 20 One might

conclude that the unhappy, the asocial, and the depressed are the ones most likely

to become ill. But clinical studies show that most cancers strike blindly and

progress despite mood, personality, or conscious efforts to remain healthy.

At this time, there is no single valid measure of immune competence. There

are indirect indices, including simple blood counts and skin tests related in complex

ways to overall ability to resist some diseases, mainly infectious. We also

know that prolonged stress, fatigue, starvation, etc., can temporarily alter the

level of some components of the NIS. But there is no convincing evidence relating

such changes to cancer.

It is important to recognize that evidence against an anticancer surveillance

role for the NIS is based on research specifically designed to find a correlation between

the NIS and spontaneous tumor development. Further, there are no credible

reports in the scientific literature to support the contention that “alternative”

methods operate—on cancer or on any other disease—through an immune mech-

*Molecular chemotherapy as methotrexate can be effective at a minimum of 1 × 10 –8

Molar concentration, which is about 1 × 10 16–17 molecules of drug per dose. Several orders

of magnitude more molecules can be given in high dose chemotherapy. Although

many chemical “hits” per cell are probably necessary for effect, the difference between adequate

numbers of killing lymphocytes possibly mobilized and adequate numbers of molecules

already available in a standard dose is enormous. The normal, nonmanipulated immune

system is simply inadequate to the task, and is yet another reason why response to

the nonmanipulated NIS has not been described. (Chabner and Myers, Clinical pharmacology)


anism. Regardless of the means used to evoke an antitumor response, evidence

available from clinical and animal studies clearly shows that only after the NIS

has been attracted by some external or medical manipulation is there any recognition

by the NIS of the existence of autologous tumor cells. 21 No “alternative”

treatment has been shown to effect such recognition or cell destruction.

Evidence amassed over the past thirty years provides an answer to the question,

“Does any AM treatment stimulate the NIS and cause it to identify and destroy new

cancer cells when they appear?” The answer clearly is no. v

REFERENCES

Green: Can Alternative Treatmens Induce Immune Surveillance over Cancer in Humans? 9

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without evidence of T-cell exhaustion or systemic anergy. J Exp Med. 1997;186:229–238.

13. Joklik WK, Willett HP, Amos DB. Immunity to tumors and pregnancy. In: Zinsser Microbiology.

Norwalk, CT: Appleton-Century-Crofts; 1984.

14. Diamond WJ, Cowden WL, Goldberg, B. Alternative Medicine: A Definitive Guide to

Cancer. Tiburon, CA: Future Medicine Publishing; 1997.

15. Hellstrom J et al. Demonstration of cell mediated immunity to human neoplasms of various

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16. Green MJ et al. Regulation of the immune response to tumor antigens. J Immunology.

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17. Spiegel D. Psychological aspects of breast cancer treatment. Semin Oncol. 1997;24:1,Suppl.

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18. Diamond, Cowden, and Goldberg, Alternative Medicine.

19. Klein G et al. Evolution of tumors—a review. Nature. 1985;315:190–195.

10. Hermans IF et al. Antigen expressed on tumor cells fails to elicit and immune response,

even in the presence of increased numbers of tumor-specific cytotoxi T-lymphocyte precursors.

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11. Lanzavecchia A. Identifying strategies for immune intervention. Science.

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12. Rosenberg SA. A new era of cancer immunotherapy: converting theory to performance.

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14. Stutman O, Cuttito MJ. Natural Cell Medicated Immunity Against Tumors. Herberman RB,

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15. Sallusto F et al. Dendritic cells use macro pinocytosis and the mannose receptor to concentrate

macromolecules in the major histocompatability complex class II compartment: down regulation

by cytokines and bacterial products. J Exp Med. 1995;182:389–400.

16. Austyn JM. New insights into the mobilizaton and phagocytic activity of dendritic cells.

J Exp Med. 1996;183: 1287–1292

17. Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol.

1991;9:271–296.

18. Schuler G, Steinman RM. Dendritic cells and adjuvants for immune mediated resistance

to tumors. J Exp Med. 1997;186:1183–1187.

19. Chabner B, Myers C. Clinical pharmacology of cancer chemotherapy. In: Cancer: Principles

and Practice of Oncology, De Vita V, Hellman S, and Rosenberg SA, eds. 1993. Philadelphia, PA:

JB Lippincott.

20. Diamond, Cowden, and Goldberg, Alternative Medicine.

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